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Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.822 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 225
- Dose descriptor starting point:
- LOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 185 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 5
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
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:
- 0.833 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 900
- Dose descriptor starting point:
- LOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 750 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 5
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
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:
- 166.7 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 30
- Dose descriptor:
- other: EC3
- Value:
- 5 000
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 166.7 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 30
- Dose descriptor starting point:
- other: EC3
- Value:
- 5 000
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
- T2PHP: OECD 422 guideline GLP study, rat, oral gavage (JRF, 2022)
- TDP: OECD 422 guideline GLP study, rat, oral gavage - extended exposure (RTI 2005)
- TiTDP: OECD 408 90-Day guideline GLP study, rat, oral gavage (JRF 2019)
- TiTDP: 90-Day GLP repeated dose toxicity, rat, oral gavage, male only (LabCorp 2022)
- TiTDP: (2) OECD 414 Prenatal developmental toxicity, rat, oral gavage (JRF 2018 and 2021)
Substance Class Overview
Tris 2 -propylheptyl phosphite (T2PHP) is one of several structurally related tris alkyl phosphites. Alkyl phosphites are characterized by a phosphorus atom connected to three alkyl ester groups (oxygen connected to an alkyl chain). The closest alkyl phosphite structural analogue to T2PHP is triisodecyl phosphite (TDP). Like T2PHP, the alkyl groups on TDP are branched C10 isomers. Another close analogue is Triisotridecyl phosphite (TiTDP); the alkyl group on TiTDP are branched C13 isomers. Here are the key studies for these chemicals:
Relationship Between Alkyl Phosphites and Alkyl Alcohols
These alkyl phosphites are manufactured using a class of alkyl alcohols that have been well studied and previously accepted as a category (Long Chain Alcohols Category under the OECD SIDS program; Alkyl Alcohols C6 to C13 Category under the U. S. High Production Volume (HPV) program). The category assessment and associated use of read-across data for these alkyl alcohols is particularly relevant for the alkyl phosphites because these phosphites readily hydrolyse into the associated alcohol used in the manufacture of the phosphite – TDP to isodecanol (C10), T2PHP to 2 -propylheptanol (C10), and TiTDP to isotridecyl alcohol. Data on these alkyl alcohols provides additional information for the assessment of alkyl phosphites and also supports the concept of the alkyl phosphites being close analogues.
Acute DNELs
There were no signs of acute toxicity by either the oral, inhalation or dermal routes for TDP, nor acute oral toxicity observed for TiTDP. As such, it has been concluded that T2PHP is not acutely toxic and therefore it is not necessary or appropriate to establish acute DNELs.
Dermal Local DNELs
TDP test positive in an LLNA skin sensitisation study. The EC3 concentration was 20%. These results are being read across to T2PHP. The DNEL has derived as follows:
DNEL = EC3[%] * 250 [µg/cm²/%] / AF = 20% * 250 µg/cm²/% / 30 = 166.7 µg/cm²
Long-Term Systemic DNELs
There are several points of departure to consider for the long-term systemic DNELs for T2PHP. In the OECD 422 study on T2PHP there was a LOEL of 150 mg/kg/day for systemic toxicity (the effects observed could not be determined definitively to be adaptive or adverse) and a NOAEL of 450 mg/kg/day for reproductive and developmental toxicity and neurotoxicity. For TDP, the NOAEL is 1000 mg/kg/day (top dose) for repeat-dose, reproductive and developmental toxicity and neurotoxicity. For TiTDP, the subchronic NOAEL is 375 mg/kg/day and the developmental toxicity NOAEL is 1000 mg/kg/day.
The most conservative DNELs were derived using the LOEL of 150 mg/kg/day from the T2PHP OECD 422 study. It should be noted that while this is not a LOAEL value, it was treated as such in the DNEL calculations. This approach to deriving these DNELs should in no way be construed as considering the effects from this study to be adverse.
The inhalation and dermal DNELs were extrapolated from the oral study using standard route-to-route extrapolations and assuming 50% oral and inhalation absorption and 10% dermal absorption.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.145 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 450
- Dose descriptor starting point:
- LOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 65.3 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 10
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
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:
- 0.417 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 1 800
- Dose descriptor starting point:
- LOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 750 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 10
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
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:
- 166.7 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 30
- Dose descriptor:
- other: EC3
- Value:
- 5 000
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 166.7 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 30
- Dose descriptor starting point:
- other: EC3
- Value:
- 5 000
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 83.3 µg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 1 800
- Dose descriptor starting point:
- LOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Default (DNEL calculator)
- AF for dose response relationship:
- 3
- Justification:
- Default (DNEL calculator)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default (DNEL calculator)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default (DNEL calculator)
- AF for other interspecies differences:
- 2.5
- Justification:
- Default (DNEL calculator)
- AF for intraspecies differences:
- 10
- Justification:
- Default (DNEL calculator)
- AF for the quality of the whole database:
- 1
- Justification:
- Default (DNEL calculator)
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
See discussion under Additional Information - Workers
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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