Reaction mass of 7539-04-0 and pentaerythritol tetrakis(3-mercaptopropionate) and 2-{3-(3-mercaptopropionyl)thiopropionyl}oxymethyl-2-(3-mercaptopropionyl)oxymethyl-1,3-propanediyl bis(3-mercaptopropionate)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.35 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

18

Dose descriptor starting point:

other: NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

132.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.

Starting point: NOAEL of 150 mg/kg bw/day in a 28-day repeated dose toxicity study in rat.

Conversion of an oral NOAEL into a corrected NOAEC:

For workers (8h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV

= 150 mg/kg bw/d * 1/0.38 m³/kg/8h * 50 /100 * 6.7 m³ (8h)/10 m³ (8h)

= 150 mg/kg bw/d * 1/0.38 m³/kg/8h * 0.5 * 6.7 m³ (8h)/10 m³ (8h)

= 150 mg/kg bw/d /0.38 * 0.5* (6.7/10) = 132.2 mg/m³.

With ABS: Absorption, sRV: Standard Respiratory Volume; wRV: Worker Respiratory Volume

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure worker

AF for interspecies differences (allometric scaling):

1

Justification:

No correction for caloric demand for inhalation; is included in dose descriptor starting point

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.08 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

72

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.

Correction dermal NOAEL: 150 x 50/50^a = 150 mg/kg bw/day

^a = % oral/dermal absorption

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure worker

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.17 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

30

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

65.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.

For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEC * 1/sRVrat * ABSoral-rat /ABSinhal-human

= 150 mg/kg bw/day * 1/1.15 m³/kg * ABSoral-rat /ABSinhal-human

= 150 mg/kg bw/day * 1/1.15 m³/kg * 0.5 = 65.2 mg/m³

With ABS: Absorption, sRV: Standard Respiratory Volume; ABSoral-rat /ABSinhal-human= 50/100= 0.5.

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

1

Justification:

No correction for caloric demand for inhalation; is included in dose descriptor starting point

AF for interspecies differences (allometric scaling):

1

Justification:

No remaining differences

AF for other interspecies differences:

1

Justification:

No correction for caloric demand for inhalation; is included in dose descriptor starting point

AF for intraspecies differences:

5

Justification:

Difference in sensitivity within general population

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.

Correction dermal NOAEL: 150 mg/kg bw/day x 50/50^a = 150 mg/kg bw/day.

^a = % oral/dermal absorption

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity within general population

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not necessary, study with oral exposure

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity among general population

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

120

DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified