Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
3.5 mg/m³
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:
14 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
other: LOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

DNELs for acute exposure (local and systemic effects)

TBEP is not classified as hazardous for acute toxicity, neither is it classified as irritating to skin or eyes, or a sensitiser. According to REACH guidance Appendix R.8-8 is it therefore not necessary to derive acute DNEL values. There are no reported irritant or toxic effects relevant to high peak exposure. For <15 minutes exposures, a factor of three times the long-term DNEL can be used in line with the recommendations of

DNELs for long-term exposure (systemic effects)

Inhalation (systemic)

No repeat dose inhalation toxicity study is available for TBEP. The inhalation DNEL was calculated using the 18-week toxicity study by oral (dietary) route. The experimental NOAEC in this study was 300 ppm, corresponding to NOAEL approximately 20 mg/kg bw.

Modification of starting point:

The NOAEL (rat) 20 mg/kg was corrected to NOAEC (human) taking into account:
Bodyweight (human):   70 kg
Worker respiratory volume (wRV):10 m3
NOAEC (worker):140 mg/m3

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
Route-to-route extrapolation:1(100% absorption considered for oral)
Interspecise variability (allometric scaling rat:human):     4
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:5(default value for workers)
Exposure duration:2(default value for subchronic to chronic)
Quality of whole database:1
Overall AF:40

Worker-DNEL long-term for inhalation route-systemic:   3.5 mg/m3

Dermal (systemic)

The dermal DNEL was calculated using the 21-day dermal toxicity study. The experimental NOAEL for systemic effects in this study was 1000 mg/kg bw/day.

Modification of starting point:

No modification from experimental NOAEL (rabbit) 1000 mg/kg was required
NOAEL (human):1000 mg/kg

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
Route-to-route extrapolation:1(dermal route used, absorption rabbit & human assumed same)
Interspecies variation (allometric scaling rabbit:human): 2.4
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:5(default value for workers)
Exposure duration:6(default value for subacute to chronic)
Quality of whole database:1
Overall AF:72

Worker-DNEL long-term for dermal route-systemic: 14 mg/kg

 

DNELs for long-term exposure (local effects)

Inhalation (local)

No repeat dose inhalation toxicity study is available for TBEP. It is therefore not possible to calculate a DNEL for local effects on the respiratory system. Data on clinical effects in the acute inhalation toxicity studies indicate that exposure to 0.52 mg/l (520 mg/m3) for 4 hours resulted in minimal irritant effects (salivation, lacrimation). The worker-DNEL long-term for systemic effects by inhalation is 3.5 mg/m3. Since this DNEL is lower than the respiratory irritation threshold by a factor of 150, the long-term systemic DNEL is protective for local effects.

Worker-DNEL long-term for inhalation route-local: 3.5 mg/m3

 

Dermal (local)

The dermal DNEL was calculated using the 21-day dermal toxicity study. The experimental NOAEL for local dermal effects in this study was 10 mg/kg bw/day.

Modification of starting point:

The NOAEL (rabbit) 10 mg/kg was corrected to NOAEL (human) taking into account:
Experimental bodyweight (rabbit):        2.6 kg
Rabbit dermal surface area 2600 cm2
% body coverage: 10%
NOAEL (human):0.1 mg/cm2/day

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
Route-to-route extrapolation:1(dermal route used, absorption rabbit & human assumed same)
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:5(default value for workers)
Exposure duration:1(effects concentration dependent)
Dose-response:1(NOAEC)
Quality of whole database:1
Overall AF:5

Worker-DNEL long-term for dermal route-local:   0.02 mg/cm2/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
1 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
1 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
1 mg/m³
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
144
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
7 mg/kg bw/day
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.01 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
other: LOAEL
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.01 mg/cm²

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.25 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNELs for acute exposure (local and systemic effects)

TBEP is not classified as hazardous for acute toxicity, neither is it classified as irritating to skin or eyes, or a sensitiser. According to REACH guidance Appendix R.8-8 is it therefore not necessary to derive acute DNEL values. Acute exposures are not anticipated for the general population.

DNELs for long-term exposure (systemic effects)

Inhalation (systemic)

No repeat dose inhalation toxicity study is available for TBEP. The inhalation DNEL was calculated using the 18-week toxicity study by oral (dietary) route. The experimental NOAEC in this study was 300 ppm, corresponding to NOAEL approximately 20 mg/kg bw.

Modification of starting point:

The NOAEL (rat) 20 mg/kg was corrected to NOAEC (human) taking into account:
Bodyweight (human):   70 kg
Human respiratory volume (sRV):20 m3 (worst case 24 h)
NOAEC (general population):70 mg/m3

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
Route-to-route extrapolation:1(100% absorption considered for oral)
Interspecise variability (allometric scaling rat:human):     4
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:10(default value for general population)
Exposure duration:2(default value for subchronic to chronic)
Quality of whole database:1
Overall AF:80

General population-DNEL long-term for inhalation route-systemic:        1 mg/m3

Dermal (systemic)

The dermal DNEL was calculated using the 21-day dermal toxicity study. The experimental NOAEL for systemic effects in this study was 1000 mg/kg bw/day.

Modification of starting point:

No modification from experimental NOAEL (rabbit) 1000 mg/kg was required
NOAEL (human):1000 mg/kg

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
Route-to-route extrapolation:1(dermal route used, absorption rabbit & human assumed same)
Interspecies variation (allometric scaling rabbit:human): 2.4
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:10(default value for general population)
Exposure duration:6(default value for subacute to chronic)
Quality of whole database:1
Overall AF:144

General population-DNEL long-term for dermal route-systemic: 7 mg/kg

Oral (systemic)

The oral DNEL was calculated using the 18-week toxicity study by oral (dietary) route. The experimental NOAEC in this study was 300 ppm, corresponding to NOAEL approximately 20 mg/kg bw.

Modification of starting point:

No modification from experimental NOAEL (rabbit) 20 mg/kg was required
NOAEL (human):20 mg/kg

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
 Interspecies variation (allometric scaling rat:human):     4
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:10(default value for general population)
Exposure duration:2(default value for subchronic to chronic)
Quality of whole database:1
Overall AF:80

General population-DNEL long-term for oral route-systemic:      0.25 mg/kg

 

DNELs for long-term exposure (local effects)

Inhalation (local)

No repeat dose inhalation toxicity study is available for TBEP. It is therefore not possible to calculate a DNEL for local effects on the respiratory system. Data on clinical effects in the acute inhalation toxicity studies indicate that exposure to 0.52 mg/l (520 mg/m3) for 4 hours resulted in minimal irritant effects (salivation, lacrimation). The general population-DNEL long-term for systemic effects by inhalation is 1 mg/m3. Since this DNEL is lower than the respiratory irritation threshold by a factor of 500, the long-term systemic DNEL is protective for local effects.

General population-DNEL long-term for inhalation route-local: 1 mg/m3

 

Dermal (local)

The dermal DNEL was calculated using the 21-day dermal toxicity study. The experimental LOAEL for local dermal effects in this study was 10 mg/kg bw/day.

Modification of starting point:

The NOAEL (rabbit) 10 mg/kg was corrected to NOAEL (human) taking into account:
Experimental bodyweight (rabbit):        2.6 kg
Rabbit dermal surface area 2600 cm2
% body coverage: 10%
NOAEL (human):0.1 mg/cm2/day

Application of Assessment Factors (AF)

AFs were applied for uncertainties/variation:
Route-to-route extrapolation:1(dermal route used, absorption rabbit & human assumed same)
Interspecies variability (remaining differences):1(no indication to apply default 2.5)
Intraspecies variability:10(default value for general population)
Exposure duration:1(effects concentration dependent)
Dose-response:1 (NOAEC)
Quality of whole database:1
Overall AF:10

General population-DNEL long-term for dermal route-local:        0.01 mg/cm2/day