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

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.1 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):

25

Dose descriptor starting point:

NOAEL

Value:

85 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

102.48 mg/m³

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):

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 the workers

AF for the quality of the whole database:

1

Justification:

the database is complete

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.29 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):

100

Dose descriptor starting point:

NOAEL

Value:

85

Modified dose descriptor starting point:

NOAEL

Value:

529.31 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 TEA or LAS Na. A study is available for TEA, which is considered relevant for the toxicity of LAS TEA. However, a route-to-route extrapolation from the oral NOAEL was chosen for the derivation of the dermal DNEL, since the NOAEL of the dermal repeated dose study with TEA is much higher, than the NOAEL of the oral repeated dose study with LAS Na.

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 data base is sufficient

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

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 TEA indicate very low toxicity: in rats the oral LD50 was 2928 mg/kg bw/day, while the dermal LD50 for LAS Na and for TEA was > 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 TEA.Inhalation exposure was considered the least relevant route, and high peak exposures through inhalation are not expected to occur.

 

LAS TEA is a skin irritant (Skin Irrit. 2, H315) and damaging to the eyes (Eye Dam. 1, H318). 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 TEA. The endpoint was addressed with data from LAS Na and TEA. There are three repeated dose oral toxicity studies with LAS Na.  The lowest LOAEL is from the 6-month rat study (Yoneyama et al., 1972) with a LOAEL of 115 mg/kg bw.  The highest NOAEL below this LOAEL is from the 9-month rat study (Yoneyama et al., 1976) with NOAEL = 85 mg/kg bw. In view of the available information it is not possible to determine which single study among those is the most reliable or appropriate for the determination of a NOAEL. Therefore, based on the data from all the studies, a NOAEL of 85 mg/kg bw is proposed, which was derived from a 9- month oral study and corresponds to the NOAEL, which is closest to the lowest available oral LOAEL of 115 mg/kg bw. The NOAEL observed in the repeated dose study with TEA was much higher (1000 mg/kg bw/day) and hence, LAS Na is much more toxic than TEA. Based on this reasoning the NOAEL= 85 mg/kg bw/day from the oral repeated-dose (9 months) toxicity study with LAS Na was used for the derivation of a long-term DNEL for LAS TEA.

 

Oral NOAEL LAS Na= 85 mg/kg bw/day; the oral NOAEL for LAS TEA was calculated by scaling based on the molecular weight of the susbstance. The conversion factor from LAS Na is 1.37 and the conversion factor from TEA is 3.19. The oral NOAEL LAS TEA= 116.45 mg/kg bw/day.This oral NOAEL was used in order to extrapolate to a dermal NOAEL. There is no available information on the dermal absorption of LAS TEA, and hence, data for the dermal absorption of sodium dodecylbenzenesulfonate (CAS 25155-30-0) and of triethanolamine were used. LAS TEA is not expected to have a higher dermal uptake. The highest absorpiton rate was recorded for TEA, in an in vitro test with human skin (22%) and thus, it was used for the route-to-route extrapolation. 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 = 116.45 * (1/0.22) = 529.31 mg/kg bw.

Assessment factors used:

Allometric scaling (rat):              4     

Intraspecies (workers):             5    

Residual interspecies:                2.5  

Sub-chronic to chronic:             2    

AF total:                                   100

This results in adermal DNEL_long-term= 5.29 mg/kg bw/day.

 

Since no inhalation data are available, cause it is not the most relevant exposure route, an inhalation DNEL was also derived on a route-to route extrapolation basis. 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 TEA, LAS Na or TEA 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 = 116.45 * (1/0.38 m³/kg/d) * (1/2) *(6.7 m³/10 m³) = 102.48 mg/m³(page 27), 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-term= 4.1 mg/m³for workers.

 

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.01 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

Modified dose descriptor starting point:

NOAEC

Value:

50.63 mg/m³

AF for dose response relationship:

1

Justification:

no other uncertainties

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic

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 data base is sufficient

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.2 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

Modified dose descriptor starting point:

NOAEL

Value:

249 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 TEA or LAS Na. A study is available for TEA, which is considered relevant for the toxicity of LAS TEA. However, a route-to-route extrapolation from the oral NOAEL was chosen for the derivation of the dermal DNEL, since the NOAEL of the dermal repeated dose study with TEA is much higher, than the NOAEL of the oral repeated dose study with LAS Na.

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:

10

Justification:

DNEL for general population

Justification:

the data base is sufficient

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)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.58 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

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:

10

Justification:

DNEL derived for the general population

AF for the quality of the whole database:

1

Justification:

the database is complete

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

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.

Acute toxicity data for LAS TEA indicate very low toxicity: in rats the oral LD50 was 2928 mg/kg bw/day, while the dermal LD50 for LAS Na and for TEA was > 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 for the general public are considered sufficient for controlling any risks that may arise from exposure to LAS TEA.Inhalation exposure was considered the least relevant route, and high peak exposures through inhalation are not expected to occur.

 

LAS TEA is a skin irritant (Skin Irrit. 2, H319) and damaging to the eyes (Eye Dam. 1, H318). However, no dose-response data are available and hence, a DNEL cannot be derived for these endpoints.

 

Similarly, as for the workers (see explanation above) the oral NOAEL LAS Na of 85 mg/kg bw/day was used for the derivation of DNELs; the oral NOAEL for LAS TEA was calculated by scaling based on the molecular weight of the susbstance. The conversion factor from LAS Na is 1.37 and the conversion factor from TEA is 3.19. The oral NOAEL LAS TEA= 116.45 mg/kg bw/day.

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= 0.58 mg/kg bw/day.

 

The oral NOAEL for rats (116.45 mg/kg bw/day) was used in order to extrapolate to a dermal NOAEL. There is no available information on the dermal absorption of LAS TEA, and hence, data for the dermal absorption of sodium dodecylbenzenesulfonate (CAS 25155-30-0) and of triethanolamine were used. LAS TEA is not expected to have a higher dermal uptake. The highest absorption rate was recorded for TEA, in an in vitro test with human skin (22%) and thus, it was used for the route-to-route extrapolation. 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 = 116.45 * (1/0.22) = 529.31 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= 2.65 mg/kg bw/day.

 

Since no inhalation data are available, because it is not the most relevant exposure route, an inhalation DNEL was also derived on a route-to route extrapolation basis. 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 TEA, LAS Na or TEA 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 = 116.45 * (1/1.15) * (1/2) = 50.63 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-term= 1.01 mg/m³

 

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