Didodecyl 3,3'-thiodipropionate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

24.7 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):

25

Dose descriptor starting point:

NOAEL

Value:

350 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

617.1 mg/m³

Explanation for the modification of the dose descriptor starting point:

see additional information below

AF for dose response relationship:

1

Justification:

NOAEL used as starting point (ECHA R.8)

AF for differences in duration of exposure:

2

Justification:

Standard for subchronic to chronic extrapolation (ECHA R.8)

AF for interspecies differences (allometric scaling):

1

Justification:

not required for inhalation studies

AF for other interspecies differences:

2.5

Justification:

Standard according to ECHA Guidance R.8

AF for intraspecies differences:

5

Justification:

Standard AF for worker population (ECHA R.8)

AF for the quality of the whole database:

1

Justification:

OECD Guideline, GLP study

AF for remaining uncertainties:

1

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:

17.5 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):

100

Dose descriptor starting point:

NOAEL

Value:

350 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

see additional information below.

AF for dose response relationship:

1

Justification:

NOAEL used as starting point (ECHA R.8)

AF for differences in duration of exposure:

2

Justification:

Standard for subchronic to chronic exposure (ECHA R.8)

AF for interspecies differences (allometric scaling):

4

Justification:

Standard allometry factor rat / human (ECHA R.8)

AF for other interspecies differences:

2.5

Justification:

standard according to ECHA Guidance R.8

AF for intraspecies differences:

5

Justification:

Standard AF for worker population (ECHA R.8)

AF for the quality of the whole database:

1

Justification:

OECD Guideline, GLP study (ECHA R.8)

AF for remaining uncertainties:

1

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:

no hazard identified

Additional information - workers

Worker inhalation long-term systemic:

 

Descriptor	Specification	Justification
Starting point	350 mg/kg bw/d	NOAEL from oral 90d repeated dose toxicity study
Modification	1/1	Absorption oral / inhalation (poor absorption following inhalation is expected due to physical-chemical properties of the substance)
Corrected NOAEC	350 mg/kg bw/d  x 1/0.38 x 6.7/10 = 617.1	Corrected starting point considering respiratory volume of rat in 8 hours, additional activity for workers and considering oral / inhalation absorption
Assessment factors
Interspecies differences / Allometry	1	Not required for inhalation (ECHA R.8)
Intraspecies differences	5	Standard AF for worker population (ECHA R.8)
Other interspecies differences	2.5
Exposure duration	2	Standard for subchronic to chronic extrapolation (ECHA R.8)
Dose-response	1	NOAEL used as starting point (ECHA R.8)
Quality of the database	1	OECD Guideline, GLP study (ECHA R.8)
Remaining uncertainties	1
Overall assessment factor	1 x 5 x 2.5 x 2 x 1 x 1 x 1 = 25
DNEL	= 617.1 ÷ 25 = 24.7 mg/m3

 

Worker inhalation long-term local: no hazard identified

 

Worker inhalation short-term systemic: no hazard identified

 

Worker inhalation short-term local: no hazard identified

 

Worker dermal long-term systemic:

 

Descriptor	Specification	Justification
Starting point	350 mg/kg bw/d	NOAEL from oral 90d repeated dose toxicity study
Modification	50 % / 10%	Absorption oral / dermal (based on high molecular weight and high Log POW, dermal absorption of 10% is expected)
Corrected NOAEL	350 mg/kg bw/d  x 50/10 = 1750 mg/kg bw/d	Corrected starting point considering oral / dermal absorption
Assessment factors
Interspecies differences / Allometry	4	Standard allometry factor rat / human (ECHA R.8)
Intraspecies differences	5	Standard AF for worker population (ECHA R.8)
Other interspecies differences	2.5
Exposure duration	2	Standard for subchronic to chronic exposure (ECHA R.8)
Dose-response	1	NOAEL used as starting point (ECHA R.8)
Quality of the database	1	OECD Guideline, GLP study (ECHA R.8)
Remaining uncertainties	1
Overall assessment factor	4 x 5 x 2.5 x 2 x 1 x 1 x 1 = 100
DNEL	= 1750 ÷ 100 = 17.5 mg/kg bw/d

 

Worker dermal long-term local: no hazard identified

 

Worker dermal short-term systemic: no hazard identified

 

Worker dermal short-term local: no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.1 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):

50

Dose descriptor starting point:

NOAEL

Value:

350 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

304.3 mg/m³

Explanation for the modification of the dose descriptor starting point:

please see additional information below.

AF for dose response relationship:

1

Justification:

NOAEL used as starting point (ECHA R.8)

AF for differences in duration of exposure:

2

Justification:

Standard for subchronic to chronic extrapolation (ECHA R.8)

AF for interspecies differences (allometric scaling):

1

Justification:

Not required for inhalation (ECHA R.8)

AF for other interspecies differences:

2.5

Justification:

standard according to ECHA Guidance R.8

AF for intraspecies differences:

10

Justification:

Standard AF for general population (ECHA R.8)

AF for the quality of the whole database:

1

Justification:

OECD Guideline, GLP study (ECHA R.8)

AF for remaining uncertainties:

1

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:

DNEL (Derived No Effect Level)

Value:

8.75 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):

200

Dose descriptor starting point:

NOAEL

Value:

350 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

please refer to the additional information below.

AF for dose response relationship:

1

Justification:

NOAEL used as starting point (ECHA R.8)

AF for differences in duration of exposure:

2

Justification:

Standard for subchronic to chronic extrapolation (ECHA R.8)

AF for interspecies differences (allometric scaling):

4

Justification:

Standard allometry factor rat / human (ECHA R.8)

AF for other interspecies differences:

2.5

Justification:

standard according to ECHA Guidance R.8

AF for intraspecies differences:

10

Justification:

Standard AF for general population (ECHA R.8)

AF for the quality of the whole database:

1

Justification:

OECD Guideline, GLP study (ECHA R.8)

AF for remaining uncertainties:

1

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:

1.75 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):

200

Dose descriptor starting point:

NOAEL

Value:

350 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

350 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

please refer to addtional information below.

AF for dose response relationship:

1

Justification:

NOAEL used as starting point (ECHA R.8)

AF for differences in duration of exposure:

2

Justification:

Standard for subchronic to chronic extrapolation (ECHA R.8)

AF for interspecies differences (allometric scaling):

4

Justification:

Standard allometry factor rat / human (ECHA R.8)

AF for other interspecies differences:

2.5

Justification:

standard factor according to ECHA Guidance R.8

AF for intraspecies differences:

10

Justification:

Standard AF for general population (ECHA R.8)

AF for the quality of the whole database:

1

Justification:

OECD Guideline, GLP study (ECHA R.8)

AF for remaining uncertainties:

1

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

Additional information - General Population

Consumer inhalation long-term systemic:

Descriptor	Specification	Justification
Starting point	350 mg/kg bw/d	NOAEL from oral 90d repeated dose toxicity study
Modification	1/1	Absorption oral / inhalation (poor absorption following inhalation is expected due to physical-chemical properties of the substance)
Corrected NOAEC	350 mg/kg bw/d  x 1/1.15 = 304.3	Corrected starting point considering respiratory volume of rat in 24 hours and considering oral / inhalation absorption
Assessment factors
Interspecies differences / Allometry	1	Not required for inhalation (ECHA R.8)
Intraspecies differences	10	Standard AF for general population (ECHA R.8)
Other interspecies differences	2.5
Exposure duration	2	Standard for subchronic to chronic extrapolation (ECHA R.8)
Dose-response	1	NOAEL used as starting point (ECHA R.8)
Quality of the database	1	OECD Guideline, GLP study (ECHA R.8)
Remaining uncertainties
Overall assessment factor	1 x 10 x 2.5 x 2 x 1 x 1 = 50
DNEL	= 304.3 ÷ 50 = 6.1 mg/m3

 

 

Consumer inhalation long-term local: no hazard identified

 

Consumer inhalation short-term systemic: no hazard identified

 

Consumer inhalation short-term local: no hazard identified

 

 

Consumer dermal long-term systemic:

Descriptor	Specification	Justification
Starting point	350 mg/kg bw/d	NOAEL from oral 90d repeated dose toxicity study
Modification	50 % / 10%	Absorption oral / dermal (based on high molecular weight and high Log POW, dermal absorption of 10% is expected)
Corrected NOAEL	350 mg/kg bw/d  x 50/10 = 1750 mg/kg bw/d	Corrected starting point considering rat oral / human oral absorption
Assessment factors
Interspecies differences / Allometry	4	Standard allometry factor rat / human (ECHA R.8)
Intraspecies differences	10	Standard AF for general population (ECHA R.8)
Other interspecies differences	2.5
Exposure duration	2	Standard for subchronic to chronic extrapolation (ECHA R.8)
Dose-response	1	NOAEL used as starting point (ECHA R.8)
Quality of the database	1	OECD Guideline, GLP study (ECHA R.8)
Remaining uncertainties	1
Overall assessment factor	4 x 10 x 2.5 x 2 x 1 x 1 = 200
DNEL	= 1750 ÷ 200 = 8.75 mg/kg bw/d

 

 

Consumer dermal long-term local: no hazard identified

 

Consumer dermal short-term systemic: no hazard identified

 

Consumer dermal short-term local: no hazard identified

 

 

 

Consumer oral long-term systemic:

Descriptor	Specification	Justification
Starting point	350 mg/kg bw/d	NOAEL from oral repeated dose toxicity study with Irganox PS 800
Modification	1/1	Absorption oral rat / oral human (no indication that human absorption would diverge from that of the rat)
Corrected NOAEL	350 mg/kg bw/d  x 1/1 = 350 mg/kg bw/d	Corrected starting point considering rat oral / human oral absorption
Assessment factors
Interspecies differences / Allometry	4	Standard allometry factor rat / human (ECHA R.8)
Intraspecies differences	10	Standard AF for general population (ECHA R.8)
Other interspecies differences	2.5
Exposure duration	2	Standard for subchronic to chronic extrapolation (ECHA R.8)
Dose-response	1	NOAEL used as starting point (ECHA R.8)
Quality of the database	1	OECD Guideline, GLP study (ECHA R.8)
Remaining uncertainties	1
Overall assessment factor	4 x 10 x 2.5 x 2 x 1 x 1 = 200
DNEL	= 350 ÷ 200 = 1.75 mg/kg bw/d