Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.2 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
129.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the inhalation route there is no animal study available. Therefore, oral rat data is used to calculate a corresponding air concentration for humans and a route-to-route extrapolation for systemic effects is necessary to derive the correct starting point. In the case of oral-to-inhalation the inclusion of a default factor of 2 is recommended according to chapter R.8.4.2 of the ECHA guidance on information requirements and chemical safety assessment, chapter R.8: Characterisation of dose [concentration]-response for human health (version 2.1, November 2012). According to Figure R. 8-3 in ECHA guidance R.8 additional correction is needed for scaling issues: Corrected inhalatory NOAEC = oral NOAEL * 50%/100% * 1/0.38 m³ per kg and day * 6.7 m³/10 m³ * 1.4 (based on the oral NOAEL of 105 mg/kg bw/day for systemic toxicity obtained in a 90-day feeding study on rats the starting point is calculated with 129.2 mg/m³. Differences in experimental/human exposure conditions were considered with the factor 1.4 (7 days/week in animal study versus 5 days/week for workers).

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
2
Justification:
Difference in the experimental exposure duration (= subchronic) and the duration of exposure for the population and scenario under consideration (= chronic) according to Table R.8-5 of ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already included in the route-to-route extrapolation for dose descriptor calculation as described in ECHA guidance R.8.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in ECHA guidance R.8.
AF for intraspecies differences:
5
Justification:
According to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor to be applied for intraspecies differences in workers is 5.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by ECHA guidance R.8.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
5.55 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For repeated exposure via the dermal route a 3 week dermal toxicity study is taken forward.  In this study the test substance was applied to the abraded and intact skin of rabbits for 6h/day, 5d/week over 3 weeks in doses of 100 and 1000 mg/kg bw/day. This study showed no effects of the test item that were considered of toxicological significance. No extrapolation for route is required. No differences in experimental/human exposure conditions were considered (5 days/week in animal study and for workers).

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
6
Justification:
Difference in the experimental exposure duration (= subacute) and the duration of exposure for the population and scenario under consideration (= chronic) according to Table R.8-5 of ECHA guidance R.8 is 6. This default factor is considered to be conservative since toxicity is not time dependent in the available oral studies (NOAEL subacute: 23.5 mg/kg bw/day; NOAEL subchronic: 105 mg/kg bw/day).
AF for interspecies differences (allometric scaling):
2.4
Justification:
According to Table R.8-3 of ECHA guidance R.8 the allometric scaling factor for the rabbits when compared with humans is 2.4.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in ECHA guidance R.8.
AF for intraspecies differences:
5
Justification:
According to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor to be applied for intraspecies differences in workers is 5.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by ECHA guidance R.8.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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

The main target organ of toxicity after repeated oral uptake of high doses of triphenyl phosphate in rats is the liver, with a distinct liver weight increase and minimal to slight hepatocellular hypertrophy. The overall NOAEl for repeated dose toxicity in rats is determined with 105 mg/kg bw. This value is taken forward for derivation of the inhalation systemic DNEL for workers.

Derivation of the dermal systemic DNEL for workers is based on a study on rabbis with repeated dermal exposure to triphenyl phosphate.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 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):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
45.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the inhalation route there is no animal study available. Therefore, oral rat data is used to calculate a corresponding air concentration for humans and a route-to-route extrapolation for systemic effects is necessary to derive the correct starting point. In the case of oral-to-inhalation the inclusion of a default factor of 2 is recommended according to chapter R.8.4.2 of ECHA guidance R.8. According to Figure R. 8-3 in ECHA guidance R.8 additional correction is needed for scaling issues: Corrected inhalatory NOAEC = oral NOAEL * 0.5 * 1/1.15 m³ per kg and day (based on the oral NOAEL of 105 mg/kg bw/day for systemic toxicity obtained in a 90-day feeding study on rats).

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
2
Justification:
Difference in the experimental exposure duration (= subchronic) and the duration of exposure for the population and scenario under consideration (= chronic) according to Table R.8-5 of ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already included in the route-to-route extrapolation for dose descriptor calculation as described in ECHA guidance R.8.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in ECHA guidance R.8.
AF for intraspecies differences:
10
Justification:
According to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor to be applied for intraspecies differences in the general population is 10.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by ECHA guidance R.8.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.98 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
360
Modified dose descriptor starting point:
NOAEL
DNEL value:
714 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For repeated exposure via the dermal route a 3 week dermal toxicity study is taken forward.  In this study the test substance was applied to the abraded and intact skin of rabbits for 6h/day, 5d/week over 3 weeks in doses of 100 and 1000 mg/kg bw/day. This study showed no effects of the test item that were considered of toxicological significance. No extrapolation for route is required. Differences in experimental/human exposure conditions were considered by dividing the NOAEL by 1.4 (5 days/week in animal study versus 7 days/week for the consumer).

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
6
Justification:
Difference in the experimental exposure duration (= subchronic) and the duration of exposure for the population and scenario under consideration (= chronic) according to Table R.8-5 of ECHA guidance R.8 is 6. This default factor is considered to be conservative since toxicity is not time dependent in the available oral studies (NOAEL subacute: 23.5 mg/kg bw/day; NOAEL subchronic: 105 mg/kg bw/day).
AF for interspecies differences (allometric scaling):
2.4
Justification:
According to Table R.8-3 of ECHA guidance R.8 the allometric scaling factor for the rat when compared with humans is 4.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in ECHA guidance R.8.
AF for intraspecies differences:
10
Justification:
According to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor to be applied for intraspecies differences in the General population is 10.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by ECHA guidance R.8.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
105 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Oral data from the rat are used to decide on a corresponding oral dose for humans. Therefore a route-to-route extrapolation is not necessary and the NOAEL from the rat study is used as starting point.

AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to chapter R.8.4.3.1 of ECHA guidance R.8 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
2
Justification:
Difference in the experimental exposure duration (= subchronic) and the duration of exposure for the population and scenario under consideration (= chronic) according to Table R.8-5 of ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
According to Table R.8-3 of ECHA guidance R.8 the allometric scaling factor for the rat when compared with humans is 4.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in ECHA guidance R.8.
AF for intraspecies differences:
10
Justification:
According to chapter R.8.4.3.1 of ECHA guidance R.8 the default AF to be applied for intraspecies differences in the general population is 10.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by ECHA guidance R.8.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The main target organ of toxicity after repeated oral uptake of high doses of triphenyl phosphate in rats is the liver, with a distinct liver weight increase and minimal to slight hepatocellular hypertrophy. The overall NOAEl for repeated dose toxicity in rats is determined with 105 mg/kg bw. This value is taken forward for derivation of the inhalation and oral systemic DNEL for the general population.

Derivation of the dermal systemic DNEL for the general population is based on a study on rabbis with repeated dermal exposure to triphenyl phosphate.