Dioctyl phosphonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.9 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):

75

Modified dose descriptor starting point:

NOAEC

Value:

367.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Inhalation is not the preferred route for absorption. Original value is NOAEL= 300 mg/kg bw/day (equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422). Allometric scaling from rat to human is 4. The result is multiplied by 70 kg considered as the average weight of a human being (bw) and divided by 10 m^3/person considered as the average volume that is breathed in a 8h exposure. Conclusion [(300 mg/kg bw/d / 4)*70 kg bw]/10 m^3/person= 525 mg/m^3. This value should be multiply by 0.5 (considering the oral absorption 50% in oral-to-inhalation extrapolation) and by 1.4 (considering the correction for differences between human and experimental exposure conditions, i.e. 7 days per week (experimental)/ 5 days per week (worker population)). NAEC is 367.5 mg/ m^3.

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed in ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

1

Justification:

Already considered in NOAEC calculation (Appendix R 8.2).

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

5

Justification:

Default value proposed in ECHA R.8 Guidance for worker (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

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)

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:

1.4 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):

300

Modified dose descriptor starting point:

other: NOAEL ( 300 mg/ kg bw/day) modified considering the differences between human and experimental exposure conditions.

Value:

420 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Original value NOAEL= 300 mg/kg bw/day (equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422) was multiplied by 1.4 (considering the correction for differences between human and experimental exposure conditions, i.e. 7 days per week (experimental)/ 5 days per week (worker population)). Starting point = 300 mg/ kg bw/day * 1.4 = 420 mg/ kg bw/day.

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed in ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

4

Justification:

Default value proposed in ECHA R.8 guidance ( table R 8.3)

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

5

Justification:

Default value proposed in ECHA R.8 Guidance for worker (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Dioctyl phosphonate is classified H319 (eye irr.cat.2) and H412 (Aquatic Chronic cat.3) according to the CLP Regulation (EC n.1272/2008).

The assessment is done based on NOAEL = 300 mg/kg bw/day ( equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422)

The values of DNEL calculated for workers are:

 

INHALATION ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL= 4.9 mg/m^3 (NAEC= 367.5 mg/m^3 and Overall AF= 75)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: Low hazard identified for LONG and SHORT TERM exposure based on its potential to be irritant for mucous membrane of nasopharyngeal region.

 

DERMAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 1.4 mg/kg bw/day (Starting point: 300 mg/kg bw/day (NOAEL for target substance) *1.4 = 420 mg/kg bw/day and Overall AF= 300)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: No hazard identified for LONG AND SHORT TERM exposure based on the substance is not skin irritant and there is no reason of concern for acute dermal toxicity.

 

HAZARD FOR EYES:LOCAL EFFECTS: Low hazard identified based on the substance is classified irritant to the eyes (H319).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.75 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):

150

Modified dose descriptor starting point:

NOAEC

Value:

112.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Inhalation is not the preferred route for absorption. Original value is NOAEL = 300 mg/kg bw/day (equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422). Allometric scaling from rat to human is 4. The result is multiplied by 60 kg considered as the average weight of a human being (bw) and divided by 20m^3/person considered as the average volume that is breathed by general population . Conclusion [(300 mg/kg bw/d / 4)*60 kg bw]/20 m^3/person= 225 mg/m^3. This value should be multiply by 0.5 (considering the oral absorption 50% in oral-to-inhalation extrapolation). NAEC is 112.5 mg/ m^3.

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed in ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

1

Justification:

Already considered in NOAEC calculation (Appendix R 8.2)

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

10

Justification:

Default value proposed in ECHA R.8 Guidance for general population (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

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)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 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):

600

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAEL = 300 mg/kg bw/day (equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422).

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed in ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

4

Justification:

Default value proposed in ECHA R.8 guidance ( table R 8.3).

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

10

Justification:

Default value proposed in ECHA R.8 Guidance for general population (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

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:

DNEL (Derived No Effect Level)

Value:

0.5 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):

600

Dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation. NOAEL = 300 mg/kg bw/day (equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422).

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed in ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

4

Justification:

Default value proposed in ECHA R.8 guidance ( table R 8.3).

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

10

Justification:

Default value proposed in ECHA R.8 Guidance for general population (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

Dioctyl phosphonate is classified H319 (eye irr.cat.2) and H412 (Aquatic Chronic cat.3) according to the CLP Regulation (EC n.1272/2008).

The assessment is done based on NOAEL = 300 mg/kg bw/day (equivalent to NOAEL repeated toxicity obtained by test performed according to OECD TG 422).

The values of DNEL calculated for general population are:

 

INHALATION ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL= 0.75 mg/m^3 (NAEC= 112.5 mg/m^3 and Overall AF= 150)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: Low hazard identified for LONG and SHORT TERM exposure based on its potential to be irritant for mucous membrane of nasopharyngeal region.

 

DERMAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.5 mg/kg bw/day (Starting point NOAEL for target substance= 300 mg/kg bw/day and Overall AF= 600)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: No hazard identified for LONG AND SHORT TERM exposure based on the substance is not skin irritant and there is no reason of concern for acute dermal toxicity.

 

ORAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.5 mg/kg bw/day (NOAEL for target substance= 300 mg/kg bw/day and Overall AF= 600)

b) SHORT TERM: : No hazard identified based on the substance is not classified for acute oral toxicity

 

HAZARD FOR EYES:LOCAL EFFECTS: Low hazard identified based on the substance is classified irritant to the eyes (H319).