Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.4 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):

37.5

Modified dose descriptor starting point:

NOAEC

Value:

52.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

for route extrapolation conditional decline (bw loss, decreased body weight gain and food consumption) is taken as systemic toxicity.

AF for dose response relationship:

1

Justification:

starting point is mid-dose NOAEL in a subacute (gavage) study + DRF study.

AF for differences in duration of exposure:

3

Justification:

The extrapolation factor from short term toxicity to the long-term scenario for a substance causing primary local toxicity is reduced by factor 2. For local irritation the concentration is in most cases the relevant parameter, and prolongation of exposure is expected to influence the severity of effect and morphology of changes, but not the NOAEL/NOAEC.

AF for interspecies differences (allometric scaling):

1

Justification:

allometric scaling is not applicable for inhalation

AF for other interspecies differences:

2.5

Justification:

default (not justified for local tox.)

AF for intraspecies differences:

5

Justification:

worker population

AF for the quality of the whole database:

1

Justification:

GLP compliant study data

AF for remaining uncertainties:

1

Justification:

No AF(2) for oral to inhalation extrapolation is applied as there is no scientific rational that the substance absorption by the oral route is less efficient than pullmonary absorption. Equal absorption for oral ingestion and inhalation has been assessed from physico-chemical properties of the substance.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.2 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

DNEL extrapolated from long term DNEL

Modified dose descriptor starting point:

NOAEC

Value:

52.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

for route extrapolation conditional decline (decreased body weight gain and decreased food consumption) is taken as systemic toxicity.

AF for dose response relationship:

1

Justification:

starting point is mid-dose NOAEL in a subacute (gavage) study

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable for inhalation

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

worker population

AF for the quality of the whole database:

1

Justification:

GLP compliant study data

AF for remaining uncertainties:

1

Justification:

No AF(2) for oral to inhalation extrapolation is applied as there is no scientific rational that the substance absorption by the oral route is less efficient than pullmonary absorption. Equal absorption for oral ingestion and inhalation has been assessed from physico-chemical properties of the substance.

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 mg/kg bw/day

Most sensitive endpoint:

skin irritation/corrosion

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1 800

Modified dose descriptor starting point:

LOAEL

Value:

450 mg/kg bw/day

AF for dose response relationship:

3

Justification:

starting point is low-dose LOAEL (conditional decline: bw loss, death) in a subacute dermal study

AF for differences in duration of exposure:

6

Justification:

The extrapolation factor from short term toxicity to the long-term scenario for a substance causing primary local toxicity is reduced by factor 2. For local irritation the concentration is in most cases the relevant parameter, and prolongation of exposure is expected to influence the severity of effect and morphology of changes, but not the NOAEL/NOAEC.

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

worker population

AF for the quality of the whole database:

2

Justification:

non GLP, pre-guideline test without NOAEL, but CPSC-reviewed data in rats and rabbits

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties; no AF for read-across is necessary (see read across justification)

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:

0.05 mg/cm²

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Dose descriptor:

other: NOAEL

AF for dose response relationship:

1

Justification:

MTD taken from chronic painting study in mice

AF for differences in duration of exposure:

1

Justification:

chronic NOAEL

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling to adjust for physiological based species differences is widely accepted for systemic toxic substances, but this does not apply to direct local effects.

AF for other interspecies differences:

1

Justification:

There is no evidence for differences in the general mode of action or kinetics, so there is no rational for an additional factor of 2.5 for remaining differences. This factor has no scientific basis, as the mode of action is direct chemical reactivity.

AF for intraspecies differences:

5

Justification:

worker population

AF for the quality of the whole database:

1

Justification:

MTD is considered reliable even if from non GLP, pre-guideline test; CPSC-reviewed data in mice

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties; no AF for read-across fromTHPC is necessary (see read across justification)

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

The substance is characterised by primary local toxicity (irritation or corrosion) depending on the concentration applied. No significant inhalation exposure is expected. Systemic toxicity was seen after repeated oral and dermal (read-across) exposure to high doses. In order to perform a quantitative risk assessment, a dermal long-term systemic DNEL was calculated based on the sub-acute LOAEL (THPC: conditional decline, death) in rats. The dermal long-term local DNEL was calculated based on the NOAEL (THPC) from a chronic mice study. The inhalation DNELs were extrapolated from an maternal NOAEL (conditional decline) with the substance. The latter were found to be close to the TLV-TWA (US-ACGIH) for THPC, a closely related, precursor substance.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

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:

no hazard identified

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