2'-anilino-6'-[ethyl(3-methylbutyl)amino]-3'-methylspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.33 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):

300

Modified dose descriptor starting point:

NOAEC

Value:

7 000 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no inhalation studies for this substance and the extrapolation of oral studies to other routes is the only method available.

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 120 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):

100

Modified dose descriptor starting point:

NOAEC

Value:

112 000 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no inhalation studies for this substance and the extrapolation of oral studies to other routes is the only method available.

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.33 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

300

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 120 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEC

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.33 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:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The acute dermal toxicity study returned a negative result. therefore the repeat-dose study result was used.

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

160 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):

100

Modified dose descriptor starting point:

NOAEL

Value:

16 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The acute dermal toxicity study returned a negative result. therefore the repeat-dose study result was used.

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.08 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

120

Dose descriptor:

other: NOAEL

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

1

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

40

Dose descriptor starting point:

other: NOAEL

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

1

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Although S-205 shows no indication of toxicity, a full set of DNEL's have been calculated for completeness and compliance with the TCC.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.67 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):

600

Modified dose descriptor starting point:

NOAEC

Value:

7 000 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no inhalation studies for this substance and the extrapolation of oral studies to other routes is the only method available.

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

560 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):

200

Modified dose descriptor starting point:

NOAEC

Value:

112 000 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no inhalation studies for this substance and the extrapolation of oral studies to other routes is the only method available.

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.67 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Dose descriptor:

NOAEC

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

560 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEC

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.67 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:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The acute dermal toxicity study returned a negative result. Therefore the repeat-dose study result was used.

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

160 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

1 600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The acute dermal toxicity study returned a negative result. therefore the repeat-dose study result was used.

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.04 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

240

Dose descriptor:

other: NOAEL

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

1

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

80

Dose descriptor starting point:

other: NOAEL

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

1

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.67 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:

NOAEL

Value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Results regarded as satisfactory, study Klimisch 1.

AF for differences in duration of exposure:

6

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

1

Justification:

Klimisch 1

AF for remaining uncertainties:

1

Justification:

No other uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

80 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

16 000

Explanation for the modification of the dose descriptor starting point:

Acute oral study used.

AF for dose response relationship:

1

Justification:

This is regarded satisfactory as the acute oral toxicity is a simple procedure

AF for interspecies differences (allometric scaling):

4

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for intraspecies differences:

10

Justification:

Default assessment factor from ECHA REACH guidelines.

AF for the quality of the whole database:

2

Justification:

The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). However, the study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

AF for remaining uncertainties:

1

Justification:

No other uncertainties.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Although S-205 shows no indication of toxicity, a full set of DNEL's have been calculated for completeness and compliance with the TCC.