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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.35 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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
26.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA.  A corrected starting point (inhalation NOAEC) of 26.5 mg/m3 can be calculated based on activity and breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%).  

AF for dose response relationship:
1
Justification:
Default value: starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default value: extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: already accounted for
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value: workers
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: no significant remaining uncertainties
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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/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):
300
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA.  In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default).  A corrected dermal starting point (NOAEL) of 30 mg/kg bw/day is calculated.  

AF for dose response relationship:
1
Justification:
Default value: starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Default value: extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: starting point is derived from a rat study
AF for other interspecies differences:
2.5
Justification:
Default value:
AF for intraspecies differences:
5
Justification:
Default value: workers
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: no significant remaining uncertainties
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

TMEDA has a harmonised classification for acute oral and acute inhalation toxicity in Category 4; no data are available for acute dermal toxicity. TMEDA has a harmonised classification for skin irritation in Category 1B. No skin sensitisation data are available. TMEDA was not genotoxic in two Ames tests or in a study of mammalian cell mutation.  A positive result is reported in vitro in a study of chromosomal aberration, but only at concentrations exceeding the limit concentration. Negative results are reported in vivo in two mouse bone marrow micronucleus assays. TMEDA is therefore concluded not to be genotoxic. The OECD 422 screening study determined a NOAEL of 30 mg/kg bw/day. This oral NOAEL is used as the starting point for DNEL derivation.

DNEL derivation

Inhalation DNELs

Systemic DNELs

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA. A corrected starting point (inhalation NOAEC) of 26.5 mg/m3 can be calculated based on activity and breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%). Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining differences) are used, resulting in an overall assessment factor of 75. Application of the overall assessment factor to the corrected starting point results in a long-term systemic inhalation DNEL of 0.35 mg/m3.

TMEDA is acutely toxic and has a harmonised classification for acute inhalation toxicity in Category 4. This classification does not result in TMEDA being assigned to any hazard band according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). A short-term systemic inhalation DNEL is not required.

Local DNELs

TMEDA has a harmonised classification for skin corrosion in Category 1B and is therefore defined as a moderate hazard according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). Long-term and short-term local inhalation DNELs are not derived.

Dermal DNELs

Systemic DNELs

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA. In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default). A corrected dermal starting point (NOAEL) of 30 mg/kg bw/day is calculated. Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining differences) are used, resulting in an overall assessment factor of 300. Application of the overall assessment factor to the corrected starting point results in a long-term systemic dermal DNEL of 0.1 mg/kg bw/day.

No acute dermal toxicity data are available. TMEDA is acutely toxic and has harmonised classification for acute oral and inhalation toxicity in Category 4. This classification does not result in TMEDA being assigned to any hazard band according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). A short-term systemic dermal DNEL is not required.

Local DNELs

TMEDA has a harmonised classification for skin corrosion in Category 1B and is therefore defined as a moderate hazard according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). Long-term and short-term local dermal DNELs are not derived.

Hazard for the eyes

TMEDA has a harmonised classification for skin corrosion in Category 1B and is therefore defined as a moderate hazard according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
13 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA.  A corrected starting point (inhalation NOAEC) of 13 mg/m3 can be calculated based on breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%).  

AF for dose response relationship:
1
Justification:
Default value: starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default value: extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: already accounted for
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value: general population
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: no significant remaining uncertainties
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)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA.  In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default).  A corrected dermal starting point (NOAEL) of 30 mg/kg bw/day is calculated.  

AF for dose response relationship:
1
Justification:
Default value: starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default value: extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: starting point is from a rat study
AF for other interspecies differences:
2.5
Justification:
Default value:
AF for intraspecies differences:
10
Justification:
Default value: general population
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: no significant remaining uncertainties
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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction of the starting point is not required.  

AF for dose response relationship:
1
Justification:
Default value: starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default value: extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: starting point is from a rat study
AF for other interspecies differences:
2.5
Justification:
Default value:
AF for intraspecies differences:
10
Justification:
Default value: general population
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: no significant 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:
medium hazard (no threshold derived)

Additional information - General Population

TMEDA has a harmonised classification for acute oral and acute inhalation toxicity in Category 4; no data are available for acute dermal toxicity. TMEDA has a harmonised classification for skin irritation in Category 1B. No skin sensitisation data are available. TMEDA was not genotoxic in two Ames tests or in a study of mammalian cell mutation.  A positive result is reported in vitro in a study of chromosomal aberration, but only at concentrations exceeding the limit concentration. Negative results are reported in vivo in two mouse bone marrow micronucleus assays. TMEDA is therefore concluded not to be genotoxic. The OECD 422 screening study determined a NOAEL of 30 mg/kg bw/day. This oral NOAEL is used as the starting point for DNEL derivation.

DNEL derivation

Inhalation DNELs

Systemic DNELs

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA. A corrected starting point (inhalation NOAEC) of 26.5 mg/m3 can be calculated based on breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%). Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining differences) are used, resulting in an overall assessment factor of 150. Application of the overall assessment factor to the corrected starting point results in a long-term systemic inhalation DNEL of 0.1 mg/m3.

TMEDA is acutely toxic and has a harmonised classification for acute inhalation toxicity in Category 4. This classification does not result in TMEDA being assigned to any hazard band according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). A short-term systemic inhalation DNEL is not required.

Local DNELs

TMEDA has a harmonised classification for skin corrosion in Category 1B and is therefore defined as a moderate hazard according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). Long-term and short-term local inhalation DNELs are not derived.

Dermal DNELs

Systemic DNELs

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA. In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default). A corrected dermal starting point (NOAEL) of 30 mg/kg bw/d is calculated. Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining differences) are used, resulting in an overall assessment factor of 600. Application of the overall assessment factor to the corrected starting point results in a long-term systemic dermal DNEL of 0.05 mg/kg bw/day.

No acute dermal toxicity data are available. TMEDA is acutely toxic and has harmonised classification for acute oral and inhalation toxicity in Category 4. This classification does not result in TMEDA being assigned to any hazard band according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). A short-term systemic dermal DNEL is not required.

Local DNELs

TMEDA has a harmonised classification for skin corrosion in Category 1B and is therefore defined as a moderate hazard according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). Long-term and short-term local dermal DNELs are not derived.

Oral DNELs

The relevant starting point is the NOAEL of 30 mg/kg bw/day from the oral OECD 422 screening study with TMEDA. Correction of the starting point is not required. Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining differences) are used, resulting in an overall assessment factor of 600. Application of the overall assessment factor to the corrected starting point results in a long-term systemic dermal DNEL of 0.05 mg/kg bw/day.

TMEDA is acutely toxic and has harmonised classification for acute oral toxicity in Category 4. This classification does not result in TMEDA being assigned to any hazard band according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016). A short-term systemic dermal DNEL is not required.

Hazard for the eyes

TMEDA has a harmonised classification for skin corrosion in Category 1B and is therefore defined as a moderate hazard according to Table E.3-1 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment (v2.0, May 2016).