Dioctadecyl disulphide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

105.8 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):

5

Modified dose descriptor starting point:

NOAEC

Value:

528.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors

AF for dose response relationship:

1

Justification:

NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.

AF for differences in duration of exposure:

1

Justification:

relevant NOAEL is derived from a chronic toxicity study (130 weeks oral toxicity study)

AF for interspecies differences (allometric scaling):

1

Justification:

interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for other interspecies differences:

1

Justification:

interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for intraspecies differences:

5

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 289.5 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Modified dose descriptor starting point:

NOAEC

Value:

26 447.4 mg/m³

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.

AF for interspecies differences (allometric scaling):

1

Justification:

Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for other interspecies differences:

1

Justification:

Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for intraspecies differences:

5

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15 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):

20

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.

AF for differences in duration of exposure:

1

Justification:

relevant NOAEL is derived from a chronic toxicity study (130 weeks oral toxicity study)

AF for interspecies differences (allometric scaling):

4

Justification:

according to Guidance on information Chapter R.8, Table 8-3, p. 24

AF for other interspecies differences:

1

Justification:

no additional AF for interspecies differences assumed

AF for intraspecies differences:

5

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

750 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

20

Modified dose descriptor starting point:

NOAEL

Value:

15 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.

AF for interspecies differences (allometric scaling):

4

Justification:

according to Guidance on information Chapter R.8, Table 8-3, p. 24

AF for other interspecies differences:

1

Justification:

no additional AF for interspecies differences assumed

AF for intraspecies differences:

5

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

please refer to "justification and comments" of each hazard point

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

26.1 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):

10

Modified dose descriptor starting point:

NOAEC

Value:

260.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.

AF for differences in duration of exposure:

1

Justification:

relevant NOAEL is derived from a chronic toxicity study (130 weeks oral toxicity study)

AF for interspecies differences (allometric scaling):

1

Justification:

interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for other interspecies differences:

1

Justification:

interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for intraspecies differences:

10

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 304.4 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Value:

13 043.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.

AF for interspecies differences (allometric scaling):

1

Justification:

Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for other interspecies differences:

1

Justification:

Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")

AF for intraspecies differences:

10

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.5 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):

40

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.

AF for differences in duration of exposure:

1

Justification:

relevant NOAEL is derived from a chronic toxicity study (130 weeks oral toxicity study)

AF for interspecies differences (allometric scaling):

4

Justification:

according to Guidance on information Chapter R.8, Table 8-3, p. 24

AF for other interspecies differences:

1

Justification:

no additional AF for interspecies differences assumed

AF for intraspecies differences:

10

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

375 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

15 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The orginal study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.

AF for dose response relationship:

1

Justification:

Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.

AF for interspecies differences (allometric scaling):

4

Justification:

according to Guidance on information Chapter R.8, Table 8-3, p. 24

AF for other interspecies differences:

1

Justification:

no additional AF for interspecies differences assumed

AF for intraspecies differences:

10

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.5 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):

40

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

n.a.; most sensitive endpoint study is repeated dose oral toxicity study

AF for dose response relationship:

1

Justification:

NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.

AF for differences in duration of exposure:

1

Justification:

relevant NOAEL is derived from a chronic toxicity study (130 weeks oral toxicity study)

AF for interspecies differences (allometric scaling):

4

Justification:

according to Guidance on information Chapter R.8, Table 8-3, p. 24

AF for other interspecies differences:

1

Justification:

no additional AF for interspecies differences assumed

AF for intraspecies differences:

10

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

375 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

15 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

n.a.; most sensitive endpoint study is acute oral toxicity study

AF for dose response relationship:

1

Justification:

Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.

AF for interspecies differences (allometric scaling):

4

Justification:

according to Guidance on information Chapter R.8, Table 8-3, p. 24

AF for other interspecies differences:

1

Justification:

no additional AF for interspecies differences assumed

AF for intraspecies differences:

10

Justification:

according to Guidance on information Chapter R.8, Table 8-6, p. 32

AF for the quality of the whole database:

1

Justification:

Original study is reliable

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

please refer to "justification and comments" of each hazard point