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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.9 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
BMDL05
Value:
55.2 mg/kg bw/day
Modified dose descriptor starting point:
BMCL05
Value:
136 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
470 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
Dose descriptor starting point:
other: methanol OEL
Value:
260 mg/m³
Modified dose descriptor starting point:
other: TMBX OEL
Value:
470 mg/m³
Explanation for the modification of the dose descriptor starting point:

The OEL for methanol has been used to derive a DNEL of 470mg/m3 for TMBX, based upon the molar proportion of methanol present following the hydrolysis of TMBX predicted in physiological fluids.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
470 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
Dose descriptor:
other: methanol OEL
Value:
260 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
470 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: TMBX DNEL derived from methanol OEL
Dose descriptor starting point:
other: methanol OEL
Value:
260 mg/m³

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
72.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
Dose descriptor starting point:
other: OEL
Value:
260 mg/m³
Modified dose descriptor starting point:
other: methanol dermal systemic DNEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Exposure to 260 mg/m³ during a working shift is roughly equivalent to a dose of 2.6 g/person/day (40 mg/kg bw/ day) which may be considered as a systemic DNEL (40 mg/kg bw/day), too, if the dermal uptake is the same as from inhalation (which is a worst-case consideration neglecting also the high volatility of the material). The dermal systemic DNEL for methanol (40 mg/kg bw/day) has been used to derive a DNEL for TMBX, based upon the molar proportion of methanol present following the hydrolysis of TMBX predicted in physiological fluids.

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
72.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: methanol OEL
Value:
260 mg/m³
Modified dose descriptor starting point:
other: methanol dermal systemic DNEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Exposure to 260 mg/m³ during a working shift is roughly equivalent to a dose of 2.6 g/person/day (40 mg/kg bw/ day) which may be considered as a systemic DNEL (40 mg/kg bw/day), too, if the dermal uptake is the same as from inhalation (which is a worst-case consideration neglecting also the high volatility of the material). The dermal systemic DNEL for methanol (40 mg/kg bw/day) has been used to derive a DNEL for TMBX, based upon the molar proportion of methanol present following the hydrolysis of TMBX predicted in physiological fluids.

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high 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:
1.92 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
BMDL05
Value:
55.2 mg/kg bw/day
Modified dose descriptor starting point:
BMCL05
Value:
48 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
93.98 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: methanol OEL
Value:
260 mg/m³
Modified dose descriptor starting point:
other: TMBX DNEL
Value:
470 mg/m³
Explanation for the modification of the dose descriptor starting point:

Exposure to 260 mg/m³ during a working shift is roughly equivalent to a dose of 2.6 g/person/day (40 mg/kg bw/ day) which may be considered as a systemic DNEL (40 mg/kg bw/day), too, if the dermal uptake is the same as from inhalation (which is a worst-case consideration neglecting also the high volatility of the material). The dermal systemic DNEL for methanol (40 mg/kg bw/day) has been used to derive a DNEL for TMBX, based upon the molar proportion of methanol present following the hydrolysis of TMBX predicted in physiological fluids.

AF for intraspecies differences:
5
Justification:
An uncertainty factor of 5 was applied for the differences between worker exposure and the general population.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
93.98 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: TMBX OEL calculated from methanol OEL
Overall assessment factor (AF):
5
Dose descriptor:
other: Methanol OEL
Value:
260 mg/m³
AF for intraspecies differences:
5
Justification:
An uncertainty factor of 5 was applied for the differences between worker exposure and the general population.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
93.98 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: TMBX OEL calculated from methanol OEL
Overall assessment factor (AF):
5
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: Methanol OEL
Value:
260 mg/m³
AF for intraspecies differences:
5
Justification:
An uncertainty factor of 5 was applied for the differences between worker exposure and the general population.

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.5 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: Methanol OEL
Value:
260 mg/m³
Modified dose descriptor starting point:
other: Methanol dermal systemic DNEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Exposure to 260 mg/m³ during a working shift is roughly equivalent to a dose of 2.6 g/person/day (40 mg/kg bw/ day) which may be considered as a systemic DNEL (40 mg/kg bw/day), too, if the dermal uptake is the same as from inhalation (which is a worst-case consideration neglecting also the high volatility of the material). The dermal systemic DNEL for methanol (40 mg/kg bw/day) has been used to derive a DNEL for TMBX, based upon the molar proportion of methanol present following the hydrolysis of TMBX predicted in physiological fluids.

AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.5 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TMBX DNEL calculated from methanol OEL
Overall assessment factor (AF):
5
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
other: Methanol OEL
Value:
260 mg/m³
Modified dose descriptor starting point:
other: Methanol dermal systemic DNEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Exposure to 260 mg/m³ during a working shift is roughly equivalent to a dose of 2.6 g/person/day (40 mg/kg bw/ day) which may be considered as a systemic DNEL (40 mg/kg bw/day), too, if the dermal uptake is the same as from inhalation (which is a worst-case consideration neglecting also the high volatility of the material). The dermal systemic DNEL for methanol (40 mg/kg bw/day) has been used to derive a DNEL for TMBX, based upon the molar proportion of methanol present following the hydrolysis of TMBX predicted in physiological fluids.

AF for intraspecies differences:
5

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.552 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
BMDL05
Value:
55.2 mg/kg bw/day
Value:
55.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.552 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
BMDL05
Value:
55.2 mg/kg bw/day
Modified dose descriptor starting point:
BMDL05
Value:
55.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of the ponit of departure is required as considering the same route of exposure

AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population