Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.16 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):
50
Dose descriptor starting point:
NOAEL
Value:
430 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
758.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. Absorption via the oral route for rat is assumed to be 100% based on absorption data via the oral route for the anionic surfactant category and via the inhalation route for humans is assumed to be 100 % as worse case. Thus, The NOAEL(oral) was converted into a NOAEC(inhalation) using the equation described in Figure R. 8-3 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012).

To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8 h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8 h exposure period).

The corrected dose descriptor for inhalation is determined using the following equation:

Corrected Inhalatory NOAEC = 1/SRVrat x ABS(oral-rat)/ABS(inh-human) x sRVhuman/wRV

= [430 mg/kg bw/day] x  [1/0.38 m3/kg bw/day] x 1 x [6.7 m3/10m3] ^

^ the equation presented in R.8 was modified based on evidence that oral absorption is effectively 100 %, meaning that the default assumption of inhalation absorption being more efficient than oral absorption is not relevant.

Thus, the corrected dose descriptor for inhalation is 758.2 mg/m3 for workers.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Default factor for a sub-chronic study. Table R.8-5 ECHA REACH Guidance.
AF for interspecies differences (allometric scaling):
1
Justification:
Table R.8-4 ECHA REACH Guidance. Assessment factor not to be used for inhalation route since the differences in the metabolic rate/bw has already been taken into account in the corrected dose descriptor.
AF for other interspecies differences:
2.5
Justification:
Table R.8-4 ECHA REACH Guidance. Assessment factor not to be used for inhalation route since the differences in the metabolic rate/bw has already been taken into account in the corrected dose descriptor.
AF for intraspecies differences:
5
Justification:
Default factor for worker. Table R.8-6 ECHA REACH Guidance.
AF for the quality of the whole database:
2
Justification:
Additional factor accounting for read across data of good/standard quality of the database taking into account completeness of the standard information requirements for the tonnage band.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

In accordance with Annex VIII, Section 8.5.2, Column 2 of REACH, testing by the inhalation route was waived due to low vapour pressure and a use pattern resulting in exposure to humans being considered negligible.  No acute toxicity is required under Regulation (EC) 1907/2006, Annex VIII, Part 8.3/8.5, Column 2 based on the test item being classified as corrosive to the skin and eye, Cat. 1B and Cat 1 according to GHS and CLP regulation.  Therefore, no acute inhalation hazard is identified for this substance.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
215 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):
200
Dose descriptor starting point:
NOAEL
Value:
430 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
43 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For systemic hazard assessment via the dermal route of exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. As available data on the dermal penetration of alkane sulfonates and alkyl sulfates indicate that less than 1% of the applied dose is adsorbed. On this basis, the oral NOAEL is divided by a factor of 0.01 to take into account the differences in absorption between the two routes. This results in a NOAEL after route to route extrapolation of 43000 mg/kg bw/day in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012).

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
AF for differences in duration of exposure:
2
Justification:
Default factor for a sub-acute study. Table R.8-5 ECHA REACH Guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default factor for worker. Table R.8-6 ECHA REACH Guidance.
AF for the quality of the whole database:
2
Justification:
Additional factor accounting for read across data of good/standard quality of the database taking into account completeness of the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

NOAEL (systemic toxicity) = 430 mg/kg bw/day; OECD 408; Walker (1967)

Sub-chronic systemic hazard assessment for this substance is based on a repeated dose toxicity study conducted on rats in accordance with OECD 408 (Walker 1967).  The substance was administered to 12 male and 12 female Carworth Farm ‘E’ strain rats via dietary intake at dose levels of 140, 200, 1000 and 5000 ppm for up to 13 weeks.  Although there was no recovery phase, this is not a guideline requirement.  The key findings in this study were significant increases in absolute organ weights which were confined to the highest test group (5000 ppm - 430 mg/kg bw/day) however only the increased liver weights from the females were found to be statistically significant (p ≤ 0.05), these were unaccompanied by any pathological effects. Therefore, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was 430 mg/kg.

In another study, OECD 414 – Palmer 1975 - Alcohol sulphate was examined for potential teratogenic and embryotoxic activity in rabbits. The test item was administered by oral gavage during days 6-18 pregnancy. Dosages employed were 0.2, 2.0, 300 and 600 mg/kg/day with each group consisting of 13 female individuals (New Zealand White). Key findings were confined to the highest dose; maternal toxicity in form of disturbance of the gastrointestinal tract, resulting in diarrhoea, anorexia, weight loss and cachexia prior to death and increase in foetal loss and reduced litter size, due almost entirely to total litter losses. These factors were deemed to be a secondary consequence of the maternal reaction to the test item, indicated by the fact that among the rabbits bearing young at termination litter parameters were comparable to the control group.

The hazard conclusion for reproductive and developmental toxicology were as follows (OECD 414, Palmer, 1975):

NOAEL(fertility) = > 600 mg/kg bw/day

NOAEL(development) > 600 hazard identified

The lowest NOAEL that could be determined for maternal toxicity was 300 mg/kg/day based on adverse clinical signs and mortality observed in the 600 mg/kg/day group.

The NOAEL used for the derivation of the DNEL was based on the OECD 408, given the sub-chronic nature of the exposure scenario, compared to that of the OECD 414.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.74 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):
100
Dose descriptor starting point:
NOAEL
Value:
430 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
374 mg/m³
Explanation for the modification of the dose descriptor starting point:

Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. Absorption via the oral route for rat is assumed to be 100% based on absorption data via the oral route for the anionic surfactant category and via the inhalation route for humans is assumed to be 100 % as worse case. Thus, The NOAEL(oral) was converted into a NOAEC(inhalation) using the equation described in Figure R. 8-3 of the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012).

To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8 h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8 h exposure period).

The corrected dose descriptor for inhalation is determined using the following equation:

Corrected Inhalatory NOAEC = 1/SRVrat x ABS(oral-rat)/ABS(inh-human) x sRVhuman/wRV

= [430 mg/kg bw/day] X  [1/0.38 m3/kg bw/day] X1X [6.7 m3/10m3] ^

^ the equation presented in R.8 was modified based on evidence that oral absorption is effectively 100 %, meaning that the default assumption of inhalation absorption being more efficient than oral absorption is not relevant.

Thus, the corrected dose descriptor for inhalation is 374 mg/m3 for workers.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
AF for differences in duration of exposure:
2
Justification:
Default factor for a sub-chronic. Table R.8-5 ECHA REACH Guidance.
AF for interspecies differences (allometric scaling):
1
Justification:
Table R.8-4 ECHA REACH Guidance. Assessment factor not to be used for inhalation route since the differences in metabolic rate/bw has already been taken into account for the corrected dose descriptor.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for general population. Table R.8-6 ECHA REACH Guidance.
AF for the quality of the whole database:
2
Justification:
Additional factor accounting for read across data of good/standard quality of the database taking into account completeness of the standard information requirements for the tonnage band.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

In accordance with Annex VIII, Section 8.5.2, Column 2 of REACH, testing by the inhalation route was waived due to low vapour pressure and a use pattern resulting in exposure to humans being considered negligible.  No acute toxicity is required under Regulation (EC) 1907/2006, Annex VIII, Part 8.3/8.5, Column 2 based on the the test item being classified as corrosive to the skin and eye, Cat. 1B and Cat 1 according to GHS and CLP regulation.  No acute inhalation hazard is therefore identified for this substance.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
107.5 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):
400
Dose descriptor starting point:
NOAEL
Value:
430 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
43 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For systemic hazard assessment via the dermal route of exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. As available data on the dermal penetration of alkane sulfonates and alkyl sulfates indicate that less than 1% of the applied dose is adsorbed. On this basis, the oral NOAEL is divided by a factor of 0.01 to take into account the differences in absorption between the two routes. This results in a NOAEL after route to route extrapolation of 43000 mg/kg bw/day in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (2012).

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Default factor for a sub-chronic. Table R.8-5 ECHA REACH Guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for general population. Table R.8-6 ECHA REACH Guidance.
AF for the quality of the whole database:
2
Justification:
Additional factor accounting for read across data of good/standard quality of the database taking into account completeness of the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

OECD 431 study (2017) - tissues were exposed to the test item for 60 minutes. Mean viability of tissues exposed to the test substance after 3 and 60 minutes were 88 % and 4.2 %, respectively. The quality criteria required for acceptance of the results was met and the test substance is considered to be corrosive to the skin in accordance with optional UN GHS sub-category 1B in accordance with UN GHS and EU CLP regulation. In accordance with the Regulation (EC) 1907/2006, Annex VIII, Part 8.3/8.5, Column 2 based on the test item being classified as corrosive to the skin and eye, Cat. 1B according to GHS and CLP regulation, no in vivo acute/short term toxicity was determined. Therefore, no acute systemic dermal hazard is identified for this substance.

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.075 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):
400
Dose descriptor starting point:
NOAEL
Value:
430 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
430 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of the dose descriptor starting point is required. The endpoint used to derive the DNEL uses the oral route for exposure.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance.
AF for differences in duration of exposure:
2
Justification:
Default factor for a sub-chronic. Table R.8-5 ECHA REACH Guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rats. Table R.8-4 ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for good/standard quality of the database taken into account completeness of the standard information requirements for the tonnage band.
AF for the quality of the whole database:
2
Justification:
Additional factor accounting for read across data of good/standard quality of the database taking into account completeness of the standard information requirements for the tonnage band.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

NOAEL (systemic toxicity) = 430 mg/kg bw/day; OECD 408; Walker (1967)

Sub-chronic systemic hazard assessment for this substance is based on a repeated dose toxicity study conducted on rats in accordance with OECD 408 (Walker 1967) .  The substance was administered to 12 male and 12 female Carworth Farm ‘E’ strain rats via dietary intake at dose levels of 140, 200, 1000 and 5000 ppm for up to 13 weeks.  Although there was no recovery phase, this is not a guideline requirement.  The key findings in this study were significant increases in absolute organ weights were confined to the highest test group (5000 ppm - 430 mg/kg bw/day) however only the increased liver weights from the females were found to be statistically significant (p ≤ 0.05), these were unaccompanied by any pathological effects. Therefore, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was 430 mg/kg.

In another study, OECD 414 – Palmer 1975 - Alcohol sulphate was examined for potential teratogenic and embryotoxic activity in rabbits. The test item was administered by oral gavage during days 6-18 pregnancy. Dosages employed were 0.2, 2.0, 300 and 600 mg/kg/day with each group consisting of 13 female individuals (New Zealand White). Key findings were confined to the highest dose; maternal toxicity in form of disturbance of the gastrointestinal tract, resulting in diarrhoea, anorexia, weight loss and cachexia prior to death and increase in foetal loss and reduced litter size, due almost entirely to total litter losses. These factors were deemed to be a secondary consequence of the maternal reaction to the test item, indicated by the fact that among the rabbits bearing young at termination litter parameters were comparable to the control group.

The hazard conclusion for reproductive and developmental toxicology were as follows (OECD 414, Palmer, 1975):

NOAEL(fertility) = > 600 mg/kg bw/day

NOAEL(development) > 600 hazard identified

The lowest NOAEL that could be determined for maternal toxicity was 300 mg/kg/day based on adverse clinical signs and mortality observed in the 600 mg/kg/day group.

The NOAEL used for the derivation of the DNEL was based on the OECD 408, given the sub-chronic nature of the exposure scenario, compared to that of the OECD 414.