2,2'-Iminodiethanol, propoxylated

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

98 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC 2003

Overall assessment factor (AF):

18

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

1 763 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The NAEC worker (8h) was calculated as prescribed by the guidance:

Corrected inhalatory NOAEC = rat oral NOAEL x (1/sRVrat) x (ABSoral rat/human inhal) x (sRVhuman/wRV)

 

-       N = 1000 x (1/0.38) x 1 x (6.7/10)

-       N= 1000 x 2.63 x 0.67 = 1763 mg/m³.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for differences in duration of exposure:

6

Justification:

Conversion from a sub-acute study to a chronic study = 6. ECETOC document (2003).

AF for interspecies differences (allometric scaling):

1

Justification:

ECETOC document (2003).

AF for other interspecies differences:

1

Justification:

ECETOC document (2003).

AF for intraspecies differences:

3

Justification:

ECETOC document (2003).

AF for the quality of the whole database:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for remaining uncertainties:

1

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:

13.9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC 2003

Overall assessment factor (AF):

72

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. In a first step a route-to-route extrapolation is made for the rat. On the assumption that, in general, dermal absorption will not be higher than oral absorption (default factor = 1) no modification of the dose descriptor is necessary to set the correct starting point when performing oral-to-dermal extrapolation

 

Oral NOAEL (rat) = dermal NOAEL(rat) = 1000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for differences in duration of exposure:

6

Justification:

Conversion from a sub-acute study to a chronic study = 6. ECETOC document (2003).

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

4

Justification:

ECETOC document (2003).

AF for intraspecies differences:

3

Justification:

ECETOC document (2003).

AF for the quality of the whole database:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

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

Acute toxicity

Diethanolamine, propoxylated is not classified for acute toxicity. Therefore, no DNEL has to be derived.

 

 

Skin and eye irritation

Diethanolamine, propoxylated is not classified for skin irritation. Therefore, no DNEL has to be derived.

 

Diethanolamine, propoxylated is not classified for eye irritation.

 

 

Skin sensitisation

Diethanolamine, propoxylated is not classified for skin sensitisation.

 

 

Repeated dose toxicity

 

a.      Worker-DNEL long-term dermal, systemic

 

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. In a first step a route-to-route extrapolation is made for the rat. On the assumption that, in general, dermal absorption will not be higher than oral absorption (default factor = 1) no modification of the dose descriptor is necessary to set the correct starting point when performing oral-to-dermal extrapolation

 

Oral NOAEL (rat) = dermal NOAEL(rat) = 1000 mg/kg bw/day

 

The DNEL long-term dermal, systemic is calculated by applying assessment factors to the NOAEL. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.

For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 72 was calculated using the ECETOC document (2003):

-       Inter-species differences = 4

-       Intra-species differences = 3

-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6

 

Worker-DNEL long-term, dermal, systemic = 1000/72 = 13.9 mg/kg bw/day

 

 

b.     Worker-DNEL long-term inhalation, systemic

 

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The NAEC worker (8h) was calculated as prescribed by the guidance:

Corrected inhalatory NOAEC = rat oral NOAEL x (1/sRVrat) x (ABSoral rat/human inhal) x (sRVhuman/wRV)

 

-       N = 1000 x (1/0.38) x 1 x (6.7/10)

-       N= 1000 x 2.63 x 0.67 = 1763 mg/m³.

 

The DNEL long-term inhalation, systemic is calculated by applying assessment factors to the NAEC. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.

For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 18 was calculated using the ECETOC document (2003):

-       Inter-species differences = 1

-       Intra-species differences = 3

-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6

 

Worker-DNEL long-term inhalation, systemic = 1763 mg/m³/18 = 98 mg/m³

 

 

Mutagenicity and carcinogenicity

 

Diethanolamine, propoxylated is not considered mutagenic. Based on the toxicological profile of the substances, carcinogenicity is not expected.

 

 

Reproduction toxicity

 

The NOAEL for reproduction toxicity was concluded to be 1000 mg/kg bw/day (highest dose tested in OECD 421 study). As no adverse reproduction toxic effects were observed at the highest dose tested, a DNEL for reproduction toxicity is not quantifiable.

Nevertheless in case the highest dose of 1000 mg/kg bw/day will be used for a DNEL derivation this will not result in a more critical DNEL compared to the DNEL for repeated dose toxicity. When deriving a DNEL for reproduction from an OECD 421 assay an additional assessment factor of 2 to 5 should be applied. However, as the assessment factor of 6 for exposure duration (conversion from a sub-acute study to a chronic study) is not applicable for deriving a DNEL for reproduction, the extra assessment factor of 2 to 5 for lower sensitivity of the OECD 421 study does not result in a higher overall assessment factor for reproduction toxicity compared to repeated dose toxicity.

 

 

Reference

 

ECETOC (2003).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

29 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC 2003

Overall assessment factor (AF):

30

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

870 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The NAEC general population (24 h) was calculated as prescribed by the guidance:

Corrected inhalatory NAEC = rat oral NOAEL x (1/sRVrat) x (ABS oral rat/ABS inhal human)

 

-       N= 1000 x (1/1.15) x 1

-       N= 1000 x 0.87 = 870 mg/m³

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for differences in duration of exposure:

6

Justification:

Conversion from a sub-acute study to a chronic study = 6. ECETOC document (2003):

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

Justification:

ECETOC document (2003).

AF for intraspecies differences:

5

Justification:

ECETOC document (2003).

AF for the quality of the whole database:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for remaining uncertainties:

1

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:

8.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC 2003

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. In a first step a route-to-route extrapolation is made for the rat. On the assumption that, in general, dermal absorption will not be higher than oral absorption (default factor = 1) no modification of the dose descriptor is necessary to set the correct starting point when performing oral-to-dermal extrapolation.

 

Oral NOAEL (rat) = dermal NOAEL (rat) = 1000 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for differences in duration of exposure:

6

Justification:

Conversion from a sub-acute study to a chronic study = 6. ECETOC document (2003).

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

4

Justification:

ECETOC document (2003).

AF for intraspecies differences:

5

Justification:

ECETOC document (2003).

AF for the quality of the whole database:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

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:

8.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC 2003

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

AF for differences in duration of exposure:

6

Justification:

Conversion from a sub-acute study to a chronic study = 6. ECETOC document (2003).

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

4

Justification:

ECETOC document (2003).

AF for intraspecies differences:

5

Justification:

ECETOC document (2003).

AF for the quality of the whole database:

1

Justification:

The starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality.

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

Acute toxicity

The substances are not classified for acute toxicity. Therefore, no DNEL has to be derived.

 

 

Skin and eye irritation

The NLPs are not classified for skin irritation. Therefore, no DNEL has to be derived.

 

NLP #3 and 6 are classified for eye irritation. The available data do not permit a DNEL derivation. Therefore, a qualitative approach will be applied for eye irritation.

The other NLPs are not classified for eye irritation.

 

 

Skin sensitisation

NLP #6 and 15 are classified for skin sensitisation. The available data do not permit a DNEL derivation. Therefore, a qualitative approach will be applied for skin sensitisation.

The other NLPs are not classified for skin sensitisation.

 

 

Repeated dose toxicity

 

a. General population-DNEL long-term oral, systemic

 

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor.

 

The DNEL (oral) is calculated by applying assessment factors to the NOAEL. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.

For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 120 was developed using the ECETOC document (2003):

-       Inter-species differences = 4

-       Intra-species differences = 5

-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6

 

General population-DNEL long-term, oral, systemic = 1000/120 = 8.3 mg/kg bw/day

 

 

b.     General population-DNEL long-term dermal, systemic

 

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. In a first step a route-to-route extrapolation is made for the rat. On the assumption that, in general, dermal absorption will not be higher than oral absorption (default factor = 1) no modification of the dose descriptor is necessary to set the correct starting point when performing oral-to-dermal extrapolation

 

Oral NOAEL (rat) = dermal NOAEL (rat) = 1000 mg/kg bw/day

 

The DNEL (dermal) is calculated by applying assessment factors to the NAEL. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.

For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 120 was calculated using the ECETOC document (2003):

-       Inter-species differences = 4

-       Intra-species differences = 5

-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6

 

General population-DNEL long-term, dermal, systemic = 1000/120 = 8.3 mg/kg bw/day

 

 

c.      General population-DNEL long-term, inhalation, systemic

 

The NOAEL of 1000 mg/kg bw/day from the 28-day repeat dose oral study in the rat was taken as dose descriptor. The NAEC general population (24 h) was calculated as prescribed by the guidance:

Corrected inhalatory NAEC = rat oral NOAEL x (1/sRVrat) x (ABS oral rat/ABS inhal human)

 

-       N= 1000 x (1/1.15) x 1

-       N= 1000 x 0.87 = 870 mg/m³

 

The DNEL (inhalation) is calculated by applying assessment factors to the NAEC. Since the starting point for the DNEL calculation is a NOAEL and the study is of good/standard quality no default factors (i.e. factor 1) are introduced for “Issues related to dose-response” and “Quality of whole database”, respectively.

For the remaining uncertainties in extrapolation procedure and in the available data an overall assessment factor of 30 was calculated using the ECETOC document (2003):

-       Inter-species differences = 1

-       Intra-species differences = 5

-       Exposure duration: Conversion from a sub-acute study to a chronic study = 6

 

General population-DNEL long-term inhalation, systemic = 870 mg/m³/30 = 29 mg/m³

 

 

Mutagenicity and carcinogenicity

 

The substances are not considered mutagenic. Based on the toxicological profile of the substances, carcinogenicity is not expected.

 

 

Reproduction toxicity

 

The NOAEL for reproduction toxicity was concluded to be 1000 mg/kg bw/day (highest dose tested in OECD 421 study). As no adverse reproduction toxic effects were observed at the highest dose tested, a DNEL for reproduction toxicity is not quantifiable.

Nevertheless in case the highest dose of 1000 mg/kg bw/day will be used for a DNEL derivation this will not result in a more critical DNEL compared to the DNEL for repeated dose toxicity. When deriving a DNEL for reproduction from an OECD 421 assay an additional assessment factor of 2 to 5 should be applied. However, as the assessment factor of 6 for exposure duration (conversion from a sub-acute study to a chronic study) is not applicable for deriving a DNEL for reproduction, the extra assessment factor of 2 to 5 for lower sensitivity of the OECD 421 study does not result in a higher overall assessment factor for reproduction toxicity compared to repeated dose toxicity.

 

 

Reference

 

ECETOC (2003).