Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.53 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
26.45 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalation NOAEL = oral NOAEL x (1/sRVrat)[1]x (ABSoral-rat/ ABSinhl-human)

= 15 mg/kg/day x (1 / 0.38m3kg-18hr-1) x (1/1)[2]

Corrected inhalation NOAEL = 39.47 mg/m3for 8hr

 

Corrected Inhalation NOAEL (workers) = 39.47 x (sRVhuman/ wRV)[3]

= 39.47 x (6.7 / 10)

Corrected Inhalation NOAEL (workers) = 26.45 mg/m3for 8hr


[1]Standard respiratory volume (rat) = 0.38 m3/kg for 8 hours.

[2]Inhalation absorption in humans is equal to the oral absorption in rats (both assumed to be 100%).

[3]Standard respiratory volume (human) = 6.7 m3for 8 hours; worker respiratory volume = 10 m3for 8 hours.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard AF for subchronic to chronic. The fact that the duration of exposure (70 days) is less than 90 days has been addressed with the database AF.
AF for interspecies differences (allometric scaling):
1
Justification:
Already addressed in dose conversion.
AF for other interspecies differences:
2.5
Justification:
Standard AF.
AF for intraspecies differences:
5
Justification:
Standard AF.
AF for the quality of the whole database:
2
Justification:
An additional factor is being added to address the fact that the repeat-dose exposures are 70 days, less than standard 90 days exposures for this endpoint.
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:
0.15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
DNEL value:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No dermal repeated-dose studies are available. Route-to-route extrapolation was therefore used to convert the NOAEL identified in an oral study in rats (15 mg/kg/d) to an equivalent dermal NOAEL. To convert the oral NOAEL to a dermal NOAEL, the registrants assumed an oral absorption of 100% in rats and a dermal absorption of 50% in humans.

Corrected dermal NOAEL = oral NOAEL x (ABSoral-rat/ ABSdermal-human)

 = 15 mg/kg/day x (1/0.5)

Corrected dermal NOAEL = 30 mg/kg/day

Whilst there is no specific measured information on TPP dermal absorption, there is quite a bit of information on dermal absorption as it relates to Kow. At a log Kow of 6.6, TPP’s dermal absorption would be expected to be very low. We believe assuming even 50% dermal absorption is a very conservative assumption for TPP given the guidance and literature on this endpoint.  ECHA considers a default of 10% dermal absorption for substances with a log Kow >4 and the NIOSH dermal absorption model does not consider dermal absorption relavant for chemicals with log Kow >5.

The likelihood of systemic exposure from dermal exposure to TPP is further lowered by the localised skin effects, which will limit contact time and skin expsoure.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard AF for subchronic to chronic. The fact that the duration of exposure (70 days) is less than 90 days has been addressed with the database AF.
AF for interspecies differences (allometric scaling):
4
Justification:
Standard AF
AF for other interspecies differences:
2.5
Justification:
Standard AF
AF for intraspecies differences:
5
Justification:
Standard AF
AF for the quality of the whole database:
2
Justification:
An additional factor is being added to address the fact that the repeat-dose exposures are 70 days, less than standard 90 days exposures for this endpoint.
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:
11.7 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor:
other: LOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.7 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor starting point:
other: LOAEL

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Acute Systemic Effects

TPP has a lower order of acute toxicity compared to the repeat-dose study. As such, a DNEL for acute toxicity is unnecessary as the long-term DNEL will be sufficient to ensure that adverse effects do not occur. Consequently, no worker-DNELs for acute toxicity have been calculated.

DNEL for Dermal Local Effect

The basis for the local dermal DNEL is the LLNA EC3 of 1.4% (Harlan 2010). The same DNEL is provided for both acute and long-term exposure. TPP will be classified as skin irritant and a skin sensitiser, so dermal exposure to the worker should be minimal due to dermal PPE (e.g., gloves). Basis for DNEL is as follows:

DNEL = EC3[%] * 250 [µg/cm²/%] / AF = 1.4% * 250 µg/cm²/% / 30 = 11.7 µg/cm²

DNELS for Long-Term Systemic Effects

The basis for the systemic DNELs is the NOAEL of 15 mg/kg/day (rats) from the repeat dose toxicity study (Tyl 2004).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population