Phosphoric acid, mixed esters with Bu alc. and ethylene glycol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

17.6 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

Dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

176.3 mg/m³

Explanation for the modification of the dose descriptor starting point:

The original 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:

2

Justification:

according to Guidance on information Chapter R.8, Table 8-5, p. 29

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:

1 260.7 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:

6 303.3 mg/m³

Explanation for the modification of the dose descriptor starting point:

The original 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:

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 without restrictions

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Local effects

Long term exposure

Hazard assessment conclusion:

other toxicological threshold

Value:

10 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

other toxicological threshold

Value:

10 mg/m³

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:

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

Dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The original 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:

2

Justification:

according to Guidance on information Chapter R.8, Table 8-5, p. 29

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:

178.8 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:

3 575 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The original 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:

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 without restrictions

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

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:

medium hazard (no threshold derived)

Additional information - workers

Worker DNEL: Long-term/short term for inhalation route, local effects

The German VCI ("Verband der chemischen Industrie") established an inhalation DNEL for local effects for substances labelled with H318 (Risk of serious damage to eyes) of 10 mg/m3 that should be applied for long- and short-term exposure equally. The derivation of this value is fully described in Messinger (2014). Briefly, the DNEL is a generic cut-off value based on an extensive analysis of the German occupational exposure limit (OEL) values as published in TRGS 900 (“Technnische Regeln für Gefahrstoffe”) for substances that are legally classified as eye irritants. Self-classifications was not considered, since they lack a peer review of the classification assigned (Messinger, 2014).

Overall, the applicability domain of the DNEL of 10 mg/m3 for irritant substances is defined as follows (Messinger, 2014):

- The substance is not a CMR substance, a heavy metal derivative, a sensitiser and does not hydrolyse to strong acids/bases

- The substance is not very toxic by ingestion, dermal contact or inhalation.

The submission substance fulfils these criteria and the DNEL of 10 mg/m3 can be applied.

 

 

Reference 

Messinger, H. (2014): An approach for the delineation of a generic cut-off value for local respiratory tract irritation by irritating or corrosive substances as a pragmatic tool to fulfill REACH requirements, Regulatory Toxicology and Pharmacology, 3, 317-324

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.3 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):

20

Dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

87 mg/m³

Explanation for the modification of the dose descriptor starting point:

The original 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:

2

Justification:

according to Guidance on information Chapter R.8, Table 8-5, p. 29

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:

310.9 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:

3 108.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

The original 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:

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 without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

Local effects

Long term exposure

Hazard assessment conclusion:

other toxicological threshold

Value:

10 mg/m³

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

other toxicological threshold

Value:

10 mg/m³

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:

2.5 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):

80

Dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The original 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:

2

Justification:

according to Guidance on information Chapter R.8, Table 8-5, p. 29

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:

89.4 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:

3 575 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The original 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:

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 without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

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:

2.5 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):

80

Modified dose descriptor starting point:

NOAEL

Value:

200 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:

2

Justification:

according to Guidance on information Chapter R.8, Table 8-5, p. 29

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:

89.4 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:

3 575 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 without restriction

AF for remaining uncertainties:

1

Justification:

no further uncertainties assumed

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

DNEL: long-term/short-term for inhalation route, local effects

The German VCI ("Verband der chemischen Industrie") established an inhalation DNEL for local effects for substances labelled with H318 (Risk of serious damage to eyes) of 10 mg/m3 that should be applied for long- and short-term exposure equally. The derivation of this value is fully described in Messinger (2014). Briefly, the DNEL is a generic cut-off value based on an extensive analysis of the German occupational exposure limit (OEL) values as published in TRGS 900 ("Technische Regeln für Gefahrstoffe") for substances that are legally classified as eye irritants. Self-classifications were not considered, since they lack a peer review of the classification assigned (Messinger, 2014).

Overall, the applicability domain of the DNEL of 10 mg/m3 for irritant substances is defined as follows (Messinger, 2014):

- The substance is not a CMR substance, a heavy metal derivative, a sensitiser and does not hydrolyse to strong acids/bases

- The substance in not very toxic by ingestion, dermal contact or inhalation.

The submission substance fulfils these criteria and the DNEL of 10 mg/m3 (inhalation, local effects) can be applied.