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Registration Dossier
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EC number: 201-122-9 | CAS number: 78-51-3
Toxicological Summary
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
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