Registration Dossier

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.33 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Value:

83.17 mg/m³

Explanation for the modification of the dose descriptor starting point:

Since inhalation data are only available for IPA, an inhalation DNEL for LAS IPA was derived with a route-to route extrapolation, based on the chosen oral NOAEL.

Since inhalation data are only available for IPA, an inhalation DNEL was also derived on a route-to route extrapolation basis, based on the chosen oral NOAEL. In order to extrapolate from an oral NOAEL to an inhalation NOAEC, absorption needs to be taken into account. There is no available information on the toxicokinetic behavior and absorption of LAS IPA, LAS Na or IPA within the pulmonary alveoli. ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 states: "In the absence of substance-specific data on absorption, it is proposed, thus, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation". Besides the absorption, the standard respiratory volume (sRV) needs to be considered, e.g. during 8 hours light activity at work the respiratory rate becomes higher than standard. This deviation is consistent with the assumption of a total breathing volume of 10 m3for an 8-hour shift and light activity at work. In the case of 8h exposure, it is assumed that the respiratory volume is 6.7 m3/person. The extrapolation from the sRV of rat to human is performed using the default assumption of 0.38 m3/kg bw (8 hours exposure):

corrected inhalation NOAEL= oral NOAEL * (1/sRVrat) * (ABSoral-rat/ABSinh-human) * (sRVhuman/wRV)<=> corrected inhalation NOAEL = 94 * (1/0.38 m3/kg/d) * (1/2) *(6.7 m3/10 m3) = 83.17 mg/m3,

where ABS: Absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume

To derive the inhalation DNEL, the same assessment factors as for the derivation of the oral and dermal DNEL were applied, except for the allometric scalling that has been already applied for the corrected inhalation NOAEL. The overall assessment factor is 25.

This results in an inhalation DNELlong-termfor workers= 3.33 mg/m3.

AF for dose response relationship:

1

Justification:

no other uncertainties

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

incorporated in the calculation of the corrected inhalation NOAEC

AF for other interspecies differences:

2.5

Justification:

toxicokinetic/toxicodynamic differences

AF for intraspecies differences:

5

Justification:

DNEL derived for workers

AF for the quality of the whole database:

1

Justification:

the database is complete

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.94 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

94 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal repeated-dose toxicity study is available either for LAS IPA. A route-to-route extrapolation from the oral NOAEL was chosen for the derivation of the dermal DNEL.

The oral NOAEL for LAS IPA was calculated by scaling based on the molecular weight of the susbstance. The conversion factor from LAS Na is 1.11. The oral NOAEL LAS IPA is 94 mg/kg bw. This oral NOAEL for rats was used in order to extrapolate to a dermal NOAEL. There is no available information on the dermal absorption of LAS IPA, and hence,a worst case 100% absorption was applied for the Route-to-Route extrapolation. According to ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 "On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. 1) should be introduced when performing oral-to-dermal extrapolation". Hence, NOAELdermal = oral NOAEL * ABSoral-rat/ABSoral-human <=> corrected NOAEL dermal = 94 * (1/1) = 94 mg/kg bw.

The following assessment factors were applied:

Allometric scaling (rat): 4

Intraspecies (workers): 5

Residual interspecies: 2.5

Sub-chronic to chronic: 2

AF total: 100

This results in a dermal DNELlong-termfor workers= 0.94 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

no other uncertainties

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to humans

AF for other interspecies differences:

2.5

Justification:

toxicokinetic/toxicodynamic differences

AF for intraspecies differences:

5

Justification:

DNEL for workers

AF for the quality of the whole database:

1

Justification:

the database is sufficient

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Hazard assessment conclusion:

low hazard (no threshold derived)

According to ECHA’s guidance R.8 a leading DN(M)EL needs to be derived for the workers for every relevant route, duration and frequency of exposure, when this is feasible.

Acute toxicity data for LAS IPA indicate very low toxicity: in rats the oral LD50 is higher than 2000 mg/kg bw/day, while the dermal LD50 for LAS Na and for IPA when normalized for LAS IPA is also higher than 2000 mg/kg bw/day. The substance shall not be classified for oral and acute dermal toxicity, and hence no DNEL_acuteshall be derived.The long-term oral and dermal DNELs workers are considered sufficient for controlling any risks that may arise from exposure to LAS IPA. Inhalation exposure was considered the least relevant route, and high peak exposures through inhalation are not expected to occur.

LAS IPA is a skin irritant (Skin Irrit. 2, H315) and irritating to the eyes (Eye Irrit. 2, H319). However, no dose-response data are available and hence, a DNEL cannot be derived for these endpoints.

No repeated dose toxicity studies were performed with LAS IPA. The endpoint was addressed with data from LAS Na and IPA. Based on information from these two substances a NOAEL of 85 mg/kg bw (from a 9-month feeding study with LAS Na) was proposed for LAS IPA. Detailed explanation on this can be found on the repeated dose toxicity section.

The oral NOAEL for LAS IPA was calculated by scaling based on the molecular weight of the susbstance. The conversion factor from LAS Na is 1.11. The oral NOAEL LAS IPA is 94 mg/kg bw. This oral NOAEL for rats was used in order to extrapolate to a dermal NOAEL. There is no available information on the dermal absorption of LAS IPA, and hence,a worst case 100% absorption was applied for the Route-to-Route extrapolation. According to ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 "On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. 1) should be introduced when performing oral-to-dermal extrapolation". Hence, NOAELdermal = oral NOAEL * ABSoral-rat/ABSoral-human <=> corrected NOAEL dermal = 94 * (1/1) = 94 mg/kg bw.

The following assessment factors were applied:

Allometric scaling (rat): 4

Intraspecies (workers): 5

Residual interspecies: 2.5

Sub-chronic to chronic: 2

AF total: 100

This results in a dermal DNEL_long-termfor workers= 0.94 mg/kg bw/day.

Since inhalation data are only available for IPA, an inhalation DNEL was also derived on a route-to route extrapolation basis, based on the chosen oral NOAEL. In order to extrapolate from an oral NOAEL to an inhalation NOAEC, absorption needs to be taken into account. There is no available information on the toxicokinetic behavior and absorption of LAS IPA, LAS Na or IPA within the pulmonary alveoli. ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 states: "In the absence of substance-specific data on absorption, it is proposed, thus, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation". Besides the absorption, the standard respiratory volume (sRV) needs to be considered, e.g. during 8 hours light activity at work the respiratory rate becomes higher than standard. This deviation is consistent with the assumption of a total breathing volume of 10 m³for an 8-hour shift and light activity at work. In the case of 8h exposure, it is assumed that the respiratory volume is 6.7 m³/person. The extrapolation from the sRV of rat to human is performed using the default assumption of 0.38 m³/kg bw (8 hours exposure):

corrected inhalation NOAEL= oral NOAEL * (1/sRVrat) * (ABS_oral-rat/ABS_inh-human) * (sRV_human/wRV)<=> corrected inhalation NOAEL = 94 * (1/0.38 m³/kg/d) * (1/2) *(6.7 m³/10 m³) = 83.17 mg/m³,

where ABS: Absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume

To derive the inhalation DNEL, the same assessment factors as for the derivation of the oral and dermal DNEL were applied, except for the allometric scalling that has been already applied for the corrected inhalation NOAEL. The overall assessment factor is 25.

This results in an inhalation DNEL_long-termfor workers= 3.33 mg/m³.

LAS IPA is not mutagenic and is not considered carcinogenic for humans. Based on the available data, LAS IPA is not considered a reproductive and developmental toxicant.

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.82 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEC

Value:

83.17 mg/m³

Explanation for the modification of the dose descriptor starting point:

Since inhalation data are only available for IPA, an inhalation DNEL was also derived on a route-to route extrapolation basis, based on the chosen oral NOAEL. In order to extrapolate from an oral NOAEL to an inhalation NOAEC, absorption needs to be taken into account. There is no available information on the toxicokinetic behavior and absorption of LAS IPA, LAS Na or IPA within the pulmonary alveoli. ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 states: "In the absence of substance-specific data on absorption, it is proposed, thus, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation". The extrapolation from the sRV of rat to human is performed using the default assumption of 1.15 m3/kg bw (24 hours exposure). Hence:

corrected inhalation NOAEL = oral NOAEL * (1/sRVrat) * (ABSoral-rat/ ABSinh-human) <=> corrected inhalation NOAEL = 94 * (1/1.15) * (1/2) = 41 mg/m3, where ABS: Absorption; sRV: standard Respiratory Volume.

To derive the inhalation DNEL for the general public, the same assessment factors as for the derivation of the oral and dermal DNEL were applied, except for the allometric scalling that has been already applied for the corrected inhalation NOAEL.

This results in an inhalation DNELlong-termfor generl public= 0.82 mg/m3

AF for dose response relationship:

1

Justification:

no other uncertainties

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

incorporated in the corrected inhalation NOAEC

AF for other interspecies differences:

2.5

Justification:

toxicokinetic/toxicodynamic differences

AF for intraspecies differences:

10

Justification:

DNEL for the general population

AF for the quality of the whole database:

1

Justification:

the database is sufficient

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.47 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Explanation for the modification of the dose descriptor starting point:

No dermal repeated-dose toxicity study is available either for LAS IPA, LAS Na or IPA. A route-to-route extrapolation from the oral NOAEL was chosen for the derivation of the dermal DNEL.

The oral NOAEL for rats (94 mg/kg bw) was used in order to extrapolate to a dermal NOAEL. There is no available information on the dermal absorption of LAS IPA, and hence, a worst case 100% absorption was applied for the Route-to-Route extrapolation. According to ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 "On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. 1) should be introduced when performing oral-to-dermal extrapolation". Hence, NOAELdermal = oral NOAEL * ABSoral-rat/ABSoral-human <=> corrected NOAEL dermal = 94 * (1/1) = 94 mg/kg bw. The same assessment factors used for the derivation of the oral DNEL were applied. This results in a dermal DNEL long-term for general population= 0.47 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

no other uncertainties

AF for differences in duration of exposure:

2.5

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to humans

AF for other interspecies differences:

2

Justification:

toxicokinetic/toxicodynamic differences

AF for intraspecies differences:

10

Justification:

DNEL for general population

AF for the quality of the whole database:

1

Justification:

the data base is sufficient

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.47 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Value:

94 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No repeated dose toxicity studies were performed with LAS IPA. The endpoint was addressed with data from LAS Na and IPA. Based on information from these two substances a NOAEL of 85 mg/kg bw (from a 9-month feeding study with LAS Na) was proposed for LAS IPA. Detailed explanation on this can be found on the repeated dose toxicity section.

The oral NOAEL for LAS IPA was calculated by scaling based on the molecular weight of the susbstance. The conversion factor from LAS Na is 1.11. The oral NOAEL LAS IPA is 94 mg/kg bw.

Assessment factors used:

Allometric scaling (rat): 4

Intraspecies (gen. pub.): 10

Residual interspecies: 2.5

Sub-chronic to chronic: 2

AF total: 200

This results in an oral DNEL long-term for general population= 0.47 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

no other uncertainties

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to humans

AF for other interspecies differences:

2.5

Justification:

toxicokinetic/toxicodynamic differences

AF for intraspecies differences:

10

Justification:

DNEL for general population

AF for the quality of the whole database:

1

Justification:

the data base is sufficient

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

Hazard assessment conclusion:

low hazard (no threshold derived)

According to ECHA’s guidance R.8 a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, when this is feasible.

LAS IPA is a skin irritant (Skin Irrit. 2, H315) and irritating to the eyes (Eye Irrit. 2, H319). However, no dose-response data are available and hence, a DNEL cannot be derived for these endpoints.

No repeated dose toxicity studies were performed with LAS IPA. The endpoint was addressed with data from LAS Na and IPA. Based on information from these two substances a NOAEL of 85 mg/kg bw (from a 9-month feeding study with LAS Na) was proposed for LAS IPA. Detailed explanation on this can be found on the repeated dose toxicity section.

The oral NOAEL for LAS IPA was calculated by scaling based on the molecular weight of the susbstance. The conversion factor from LAS Na is 1.11. The oral NOAEL LAS IPA is 94 mg/kg bw.

Assessment factors used:

Allometric scaling (rat): 4

Intraspecies (gen. pub.): 10

Residual interspecies: 2.5

Sub-chronic to chronic: 2

AF total: 200

This results in an oral DNEL_long-termfor general population= 0.47 mg/kg bw/day.

The oral NOAEL for rats (94 mg/kg bw) was used in order to extrapolate to a dermal NOAEL. There is no available information on the dermal absorption of LAS IPA, and hence,a worst case 100% absorption was applied for the Route-to-Route extrapolation. According to ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 "On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. 1) should be introduced when performing oral-to-dermal extrapolation". Hence, NOAELdermal = oral NOAEL * ABSoral-rat/ABSoral-human <=> corrected NOAEL dermal = 94 * (1/1) = 94 mg/kg bw. The same assessment factors used for the derivation of the oral DNEL were applied. This results in a dermal DNEL_long-termfor general population= 0.47 mg/kg bw/day.

Since inhalation data are only available for IPA, an inhalation DNEL was also derived on a route-to route extrapolation basis, based on the chosen oral NOAEL. In order to extrapolate from an oral NOAEL to an inhalation NOAEC, absorption needs to be taken into account. There is no available information on the toxicokinetic behavior and absorption of LAS IPA, LAS Na or IPA within the pulmonary alveoli. ECHA’s guidance Dose [concentration]-response regarding human health R.8.4.2 pag. 25 states: "In the absence of substance-specific data on absorption, it is proposed, thus, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to-inhalation extrapolation". The extrapolation from the sRV of rat to human is performed using the default assumption of 1.15 m3/kg bw (24 hours exposure). Hence:

corrected inhalation NOAEL = oral NOAEL * (1/sRV_rat) * (ABS_oral-rat/ ABS_inh-human) <=> corrected inhalation NOAEL = 94 * (1/1.15) * (1/2) = 41 mg/m³, where ABS: Absorption; sRV: standard Respiratory Volume.

To derive the inhalation DNEL for the general public, the same assessment factors as for the derivation of the oral and dermal DNEL were applied, except for the allometric scalling that has been already applied for the corrected inhalation NOAEL.

This results in an inhalation DNEL_long-termfor generl public= 0.82 mg/m³

LAS IPA is not mutagenic and is not considered carcinogenic for humans. Based on the available data, LAS IPA is not considered a reproductive and developmental toxicant.

Registration Dossier

Registration Dossier

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Diss Factsheets

Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with 2-propanamine

Toxicological Summary

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

Workers - Hazard for the eyes

Local effects

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

General Population - Hazard via oral route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

General Population - Hazard for the eyes

Local effects

Additional information - General Population