Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.9 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
246.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the inhalation route there is no reliable 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 200 mg/kg bw/day for systemic toxicity obtained in the Guideline compliant 90-day gavage study on rats the starting point is calculated with 246.8 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).

corrected inhalatory NOAEC for workers = 246.8 mg/m³

AF for dose response relationship:
1
Justification:
Since 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 as default.
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:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
100
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
280 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the dermal route there is no reliable animal study available. Therefore, oral rat data is used to calculate a corresponding dermal dose for humans. Triethyl phosphate is well absorbed in the gastrointestinal tract. Within 16 hours in rats and mice 90% of the oral or ip applied dose was excreted via urine. On the assumption that in general dermal absorption will not be higher than oral absorption no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation (chapter 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). 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):
4
Justification:
According to Table R.8-3 of ECHA guidance R.8 the allometric scaling factor for rats 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:
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:
There is information available to cover all relevant toxicological endpoints
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

According to Appendix R.8-8 of ECHA guidance R.8 a DNEL for acute/short-term exposure should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. No Guideline conform acute dermal toxicity study is available for the substance. However, information on a dermal LD50 value in rabbits of > 20000 mg/kg bw obtained from a peer-reviewed report together with the non irritation nature of the substance and the fact that no systemic effects were reported in skin irritation studies, an acute dermal toxicity potential of the substance cannot be expected on a Weight of Evidence basis. The vapour pressure of triethyl phosphate is low and there is no potential for high peak exposures foreseen. Thus, no relevant acute/short-term hazard via inhalation route can be identified.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The main target organ of toxicity after repeated oral uptake of high doses of triethyl 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 200 mg/kg bw/day. This value is taken forward for derivation of the inhalation and dermal systemic DNEL for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.74 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
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the inhalation route there is no reliable 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 200 mg/kg bw/day for systemic toxicity obtained in a 90-day feeding study on rats).

corrected inhalatory NOAEC for the General Population = 87 mg/m³

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:
rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation
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:
There is information available to cover all relevant toxicological endpoints
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 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
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the dermal route there is no reliable animal study available. Therefore, oral rat data is used to calculate a corresponding dermal dose for humans. Triethyl phosphate is well absorbed in the gastrointestinal tract. Within 16 hours in rats and mice 90% of the oral or ip applied dose was excreted via urine. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation (ECHA guidance R.8, chapter 8.4.2). No differences in experimental/human exposure conditions were considered (7 days/week in the animal study and for the general population.

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 assessment factor to be applied for intraspecies differences in the general population is 10.
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

According to Appendix R.8-8 of ECHA guidance R.8 a DNEL for acute/short-term exposure should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. No Guideline conform acute dermal toxicity study is available for the substance. However, information on a dermal LD50 value in rabbits of > 20000 mg/kg bw obtained from a peer-reviewed report together with the non irritation nature of the substance and the fact that no systemic effects were reported in skin irritation studies, an acute dermal toxicity potential of the substance cannot be expected on a Weight of Evidence basis. The vapour pressure of triethyl phosphate is low and there is no potential for high peak exposures foreseen. Thus, no relevant acute/short-term hazard via inhalation route can be identified.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 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
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 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:
There is information available to cover all relevant toxicological endpoints
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

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 200 mg/kg bw. This value is taken forward for derivation of the inhalation, dermal and oral systemic DNEL for the general population.