Poly (dipropyleneglycol) Phenyl phosphite

Toxicological Summary

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

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

26.45 mg/m³

Explanation for the modification of the dose descriptor starting point:

Corrected inhalation NOAEL = oral NOAEL x (1/sRV_rat)[1]x (ABS_oral-rat/ ABS_inhl-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 (sRV_human/ 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:

0.375 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

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal repeated-dose studies are available. The substance is very similar to a polymer with a molecular weight in excess of 2100, though without fully meeting the polymer definition under REACH, so the expectation is that there will be very little if any, absorption and systemic exposure via the skin. Nonetheless, a route-to-route extrapolation has been done using TPP oral data, TPP is a minor constituent in D25 -207, was 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 10% in humans.

Corrected dermal NOAEL = oral NOAEL x (ABS_oral-rat/ ABS_dermal-human)

 = 15 mg/kg/day x (1/0.5)

Corrected dermal NOAEL = 30 mg/kg/day

Whilst there is no specific measured information on D25 -207 dermal absorption, there is quite a bit of information on dermal absorption as it relates to Kow and MW At a log Kow of >20 and MW >2000, D25 -207's dermal absorption would be expected to be very low. We believe assuming even 10% dermal absorption is a very conservative assumption for D25 -207 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 D25 -207 is further lowered by the localised skin effects driven by the TPP content, 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

D25 -207 has a lower order of acute toxicity. 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 from the TPP LLNA EC3 of 1.4% (Harlan 2010). The same DNEL is provided for both acute and long-term exposure. D25 -207 is classified as skin irritant and a skin sensitiser based on the TPP content, 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

Approach to DNELS for Long-Term Systemic Effects; Read-Across Justification

D25 -207 is very similar to a polymer with a molecular weight in excess of 2100, though without fully meeting the polymer definition under REACH. The available toxicology data on D25 -207, whilst limited, does not indicate a hazard potential. However, D25 -207 contains triphenyl phosphite (TPP) at a concentration of 5 -10% w/w. This TPP impurity drives the classification of this substance and thus it was decided that the use of TPP data represented a worst-case read-across for the hazard assessment of D25 -207.

The basis for the systemic DNELs on D25 -207 is the TPP repeat dose 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