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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
LOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
LOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
LOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Additional information - workers

For the inhalation, dermal and oral exposure routes, ‘short-term’ exposures will be assessed using the long-term DNELs.

Long-term inhalation route-systemic (worker) using extrapolations factors:

Calculation according to EU Draft RAR dated May 2008:

LOAEL (rat) oral: 52 mg/kg bw/day

"Normally a further factor of 3 would be used to take into account the use of a LOAEL rather than a NOAEL. However this is not considered necessary here, as the adverse effect in the repeated dose toxicity study (mainly liver weight changes are not considered particularly toxicologically significant and the LOAEL is probably quite close to the NOAEL. "

NOEL (rat) oral: 52 mg/kg bw/day

ABS oral rat=80 %

ABS inhalativ human= 100 %

80/100 =0.8

52*0.8= 41.6 mg/kg bw/d

Corrected NOAEL (rat) oral: 41.6 mg/kg bw

For interspecies differences rat vs. human 4

41.6 mg/kg: 4 = 10.4 mg/kg bw/d

Body weight worker = 70 kg bw/person

10.4 mg/kg * 70 kg bw/person= 728 mg/person/d

Respiratory volume worker = 10 m³/person (8h exposure; light activity for worker)

728 mg/person/d: 10 m³/person = 72.8 mg/m³/8h

NOEC worker (8h) = 72.8 mg/m³

For remaining interspecies 2.5

For intraspecies differences in worker 5

"A factor to allow for semi (sub) -chronic to chronic extrapolation (usually a factor of 2) was not used here. It is not considered necessary, as relatively similar effects on the liver, at doses of a comparable order of magnitude were observed in both the 28-day and the 90-day studies and so it felt that exposure duration is not significant. "

For reliability of dose response 1

For quality of whole database 1

Overall factor 12.5

Worker DNEL long-term for inhalation route-systemic = 5.82 mg/m³/8h

Long-term dermal route-systemic (worker) using extrapolation factors:

Calculation according to EU Draft RAR dated May 2008:

LOAEL (rat) oral: 52 mg/kg bw/day

"Normally a further factor of 3 would be used to take into account the use of a LOAEL rather than a NOAEL. However this is not considered necessary here, as the adverse effect in the repeated dose toxicity study (mainly liver weight changes are not considered particularly toxicologically significant and the LOAEL is probably quite close to the NOAEL. "

NOEL (rat) oral: 52mg/kg bw/day

ABS (rat) oral= 80%

ABS dermal= 40 % (foam) – this is a worst case scenario because in the EU Draft RAR dated May 2008 a total absorption value of 23% is taken forward to risk characterisation for scenarios where there is exposure to "neat" TCPP and 40% dermal absorption is taken forward for those scenarios where there is exposure due to handling of foam containing TCPP".

80:40=2

Corrected NOAEL= 104 mg/kg bw/day

For interspecies differences rat vs. human 4

For remaining interspecies differences: 2.5

For intraspecies differences in worker 5

"A factor to allow for semi (sub) -chronic to chronic extrapolation (usually a factor of 2) was not used here. It is not considered necessary, as relatively similar effects on the liver, at doses of a comparable order of magnitude were observed in both the 28-day and the 90-day studies and so it felt that exposure duration is not significant. "

For reliability of dose response 1

For quality of whole database 1

Overall factor: 50

Worker-DNEL long-term for dermal route systemic = 2.08 mg/kg bw/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
LOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.04 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
LOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.04 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
LOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
0.52 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
LOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.52 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
LOAEL

General Population - Hazard for the eyes

Additional information - General Population

For the inhalation, dermal and oral exposure routes, ‘short-term’ exposures will be assessed using the long-term DNELs.

Long-term inhalation route-systemic (general population) using extrapolations factors:

Calculation according to EU Draft RAR dated May 2008:

LOAEL (rat) oral: 52 mg/kg bw/day

"Normally a further factor of 3 would be used to take into account the use of a LOAEL rather than a NOAEL. However this is not considered necessary here, as the adverse effect in the repeated dose toxicity study (mainly liver weight changes are not considered particularly toxicologically significant and the LOAEL is probably quite close to the NOAEL. "

NOEL (rat) oral: 52 mg/kg bw/day

ABS oral rat=80 %

ABS inhalativ human= 100 %

80/100 =0.8

52*0.8= 41.6 mg/kg bw/d

Corrected NOAEL (rat) oral: 41.6 mg/kg bw

For interspecies differences rat vs. human 4

41.6 mg/kg: 4 = 10.4 mg/kg

Body weight general public = 70 kg bw/person

10.4 mg/kg * 70 kg bw/person= 728 mg/person/d

Respiratory volume general population: 20 m³/person (24h exposure; general population)

728 mg/person/d: 20 m³/person = 36.4 mg/m³/24 h

NOEC general population (24h) = 36.4 mg/m³/24h

For remaining interspecies differences: 2.5

For intraspecies differences in general population: 10

"A factor to allow for semi (sub) -chronic to chronic extrapolation (usually a factor of 2) was not used here. It is not considered necessary, as relatively similar effects on the liver, at doses of a comparable order of magnitude were observed in both the 28-day and the 90-day studies and so it felt that exposure duration is not significant. "

For reliability of dose response 1

For quality of whole database 1

Overall factor: 25

General population DNEL long-term for inhalation route systemic = 1.46 mg/m³/24 h

Long-term oral route-systemic (general population) using extrapolation factors:

Calculation according to EU Draft RAR dated May 2008:

LOAEL (rat) oral: 52 mg/kg bw/day

"Normally a further factor of 3 would be used to take into account the use of a LOAEL rather than a NOAEL. However this is not considered necessary here, as the adverse effect in the repeated dose toxicity study (mainly liver weight changes are not considered particularly toxicologically significant and the LOAEL is probably quite close to the NOAEL. "

NOEL (rat) oral: 52 mg/kg bw/day

For interspecies differences rat vs. human 4

For remaining interspecies differences: 2.5

For intraspecies differences in general population 10

"A factor to allow for semi (sub) -chronic to chronic extrapolation (usually a factor of 2) was not used here. It is not considered necessary, as relatively similar effects on the liver, at doses of a comparable order of magnitude were observed in both the 28-day and the 90-day studies and so it felt that exposure duration is not significant. "

For reliability of dose response 1

For quality of whole database 1

Overall factor: 100

General population-DNEL long-term for dermal (oral) route systemic = 0.52 mg/kg bw/d

Long-term dermal route-systemic (general population) using extrapolation factors:

Calculation according to EU Draft RAR dated May 2008:

LOAEL (rat) oral: 52 mg/kg bw/day

"Normally a further factor of 3 would be used to take into account the use of a LOAEL rather than a NOAEL. However this is not considered necessary here, as the adverse effect in the repeated dose toxicity study (mainly liver weight changes are not considered particularly toxicologically significant and the LOAEL is probably quite close to the NOAEL. "

NOEL (rat) oral: 52mg/kg bw/day

ABS (rat) oral= 80%

ABS dermal= 40% - this is a worst case scenario because in the EU Draft RAR dated May 2008 a total absorption value of 23% is taken forward to risk characterisation for scenarios where there is exposure to "neat" TCPP and 40% dermal absorption is taken forward for those scenarios where there is exposure due to handling of foam containing TCPP".

80:40=2

Corrected NOAEL= 104 mg/kg bw/day

For interspecies differences rat vs. human 4

For remaining interspecies differences: 2.5

For intraspecies differences in general population 10

"A factor to allow for semi (sub) -chronic to chronic extrapolation (usually a factor of 2) was not used here. It is not considered necessary, as relatively similar effects on the liver, at doses of a comparable order of magnitude were observed in both the 28-day and the 90-day studies and so it felt that exposure duration is not significant. "

For reliability of dose response 1

For quality of whole database 1

Overall factor: 100

General population-DNEL long-term for dermal route systemic = 1.04 mg/kg bw/d