Tetraphosphorus trisulphide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.016 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:

1.225 mg/m³

Explanation for the modification of the dose descriptor starting point:

Inhalation should not be a preferred route for absorption. Original value is NOAEL 1 mg/kg bw/day, subacute toxicity in rat by oral administration. 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 [(1 mg/kg bw/d / 4)*70 Kg bw]/10 m^3/person= 1.75 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 1.225 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 n 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:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium 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:

0.259 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 ( 1 mg/ kg bw/day) modified considering the differences between human and experimental exposure conditions and considering the experimental value of dermal absorption.

Value:

77.8 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Original value is NOAEL 1 mg/kg bw/day (subacute toxicity in rat by oral administration) 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 = 1 mg/ kg bw/day * 1.4 = 1.4 mg/ kg bw/day.

Considering the result of the skin absorption test, a correction of starting point has been performed, taking into account a skin absorption of ca.1.8 %. Therefore the starting point was: 1.4 mg/kg bw/day : 0.018 = 77.8 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 n 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 8.6).

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:

high hazard (no threshold derived)

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:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Tetraphosphorus trisulphide is classified H301 (Acute oral toxicity cat.3), H318 (Causes serious eye damage cat.1), H317 (Skin sens. cat.1) and H373 (STOT Rep. Exp. 2) according to the CLP Regulation (EC n.1272/2008). Moreover, P4S3 is high flammable solid (H228, cat.1). The test item is also classified H260 (Water React. Flam. Gas 1) and H400 (Aquatic Acute toxicity cat.1) according to Annex VI of the CLP Regulation (EC n.1272/2008) even though these classifications were not confirmed by experimental data.

The assessment is done based on estimated NOAEL (repeated oral toxicity 28 days rat)= 1 mg/kg bw/day

The values of DNEL calculated for workers are:

 

INHALATION ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL= 0.0163 mg/m^3 (NAEC= 1.225 mg/m^3 and Overall AF= 75)

b) SHORT TERM: Medium hazard identified due to the classification H301 (acute oral toxicity cat.3)

LOCAL EFFECTS: Medium hazard identified for LONG and for SHORT TERM exposure based on its potential to have adverse effects on mucous.

 

DERMAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.259 mg/kg bw/day (Starting point: [1 mg/kg bw/day (NOAEL for target substance) *1.4]: 0.018 = 77.8 mg/kg bw/day and Overall AF= 300)

b) SHORT TERM: High hazard identified due to classification H317 (skin sens. cat.1)

LOCAL EFFECTS:

a) LONG TERM: Hazard unknown but no exposure expected considering appropriate RMM and PPEs used in the workplace.

b) SHORT TERM: No hazard identified based on the substance is not skin irritant. 

HAZARD FOR EYES:LOCAL EFFECTS: Medium hazard identified due to classification H318 (eye damage cat.1).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.003 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:

0.375 mg/m³

Explanation for the modification of the dose descriptor starting point:

Inhalation should not be a preferred route for absorption. Original value is NOAEL 1 mg/kg bw/day, subacute toxicity in rat by oral administration. 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 [(1 mg/kg bw/d / 4)*60 Kg bw]/20 m^3/person= 0.75 mg/m^3. This value should be multiply by 0.5 (considering the oral absorption 50 % in oral-to-inhalation extrapolation). NAEC is 0.375 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 n 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:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium 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:

0.092 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

Modified dose descriptor starting point:

other: NOAEL ( 1 mg/ kg bw/day) modified considering the experimental value of dermal absorption.

Value:

55.55 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Original value is NOAEL 1 mg/kg bw/day, subacute toxicity in rat by oral administration.

Considering the result of the skin absorption test, a correction of starting point has been performed, taking into account a skin absorption of ca.1.8 %.

Therefore the starting point was: 1 mg/kg bw/day : 0.018 = 55.5 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 n 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 8.6).

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:

high hazard (no threshold derived)

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:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.002 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:

1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Original value is NOAEL 1 mg/kg bw/day, subacute toxicity in rat by oral administration

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 n 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 8.6).

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:

medium hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

Tetraphosphorus trisulphide is classified H301 (Acute oral toxicity cat.3), H318 (Causes serious eye damage cat.1), H317 (Skin sens. cat.1) and H373 (STOT Rep. Exp. 2) according to the CLP Regulation (EC n.1272/2008). Moreover, P4S3 is high flammable solid (H228, cat.1). The test item is also classified H260 (Water React. Flam. Gas 1) and H400 (Aquatic Acute toxicity cat.1) according to Annex VI of the CLP Regulation (EC n.1272/2008) even though these classifications were not confirmed by experimental data.

The assessment is done based on estimated NOAEL (repeated oral toxicity 28 days rat)= 1 mg/kg bw/day

The values of DNEL calculated for general population are:

 

INHALATION ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL= 0.0025 mg/m^3 (NAEC= 0.375 mg/m^3 and Overall AF= 150)

b) SHORT TERM: Medium hazard identified due to the classification H301 (acute oral toxicity cat.3)

LOCAL EFFECTS: Medium hazard identified for LONG and for SHORT TERM exposure based on its potential to have adverse effects on mucous.

 

DERMAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.092 mg/kg bw/day (Starting point :1 mg/kg bw/day (NOAEL for target substance) / 0.018= 55.55 mg/kg bw/day and Overall AF= 600)

b) SHORT TERM: High hazard identified due to classification H317 (skin sens. cat.1)

 LOCAL EFFECTS:

a) LONG TERM: Hazard unknown but no exposure expected considering the only use of Tetraphosphorus trisulphide in the matches with short exposure (about 30 min)

b) SHORT TERM: No hazard identified based on the substance is not skin irritant. 

 

ORAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.0016 mg/kg bw/day (NOAEL for target substance= 1 mg/kg bw/day and Overall AF= 600)

b) SHORT TERM: Medium hazard identified based on the substance is classified H301 (acute oral toxicity cat.3)

HAZARD FOR EYES:LOCAL EFFECTS: Medium hazard identified due to classification H318 (eye damage cat.1).