Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.26 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
Modified dose descriptor starting point:
NOAEC
Value:
881.58 mg/m³
Explanation for the modification of the dose descriptor starting point:
The dose descriptor starting point is obtained by conversion of the oral NOAEL of 500 mg/kg bw from the oral one-generation toxicity study in rats with the calcium sulfonate read-across substance, (CAS 115733-09-0), (Bjorn, 2004) to an inhalation NOAEC taking into account an oral absorption of 50 % and absorption by inhalation of 50 %, the sRV (standard respiratory volume of rats during 8 hours) of 0.38 m³/kg/day and 6.7 m³ and 10 m³ (standard respiratory volumes for workers under normal conditions and by light activity).
AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
2
Justification:
since it is a subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scalling should be applied in case of oral-to-inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default
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:
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:
25 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
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A NOAEL of 500 mg/kg bw /day from the one-generation oral repeated dose toxicity study with the calcium sulfonate read across substance, (CAS 115733-09-0), is available for rats (Bjorn, 2004). This value was converted into the corrected dermal NOAEL taking into account the rates for absorption (oral 50 %, dermal 10 %).
AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
2
Justification:
since it is a subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default factor for rats
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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:
DNEL (Derived No Effect Level)
Value:
1.04 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEL of 5.18 mg/cm²
AF for dose response relationship:
1
Justification:
Not applicable for sensitisation
AF for interspecies differences (allometric scaling):
1
Justification:
Deafult: no allometric scaling AF for local effects (skin sensitisation is a local effect)
AF for other interspecies differences:
1
Justification:
The DBEL is derived with human data.
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
Multiple reliable studies with Klimisch code 1 and 2
AF for remaining uncertainties:
1
Justification:
LOAEL to NOAEL

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The calculation of the DNELs is performed in accordance with the principles given in ECHA (2012) “Guidance of Information Requirements and Chemical Safety Assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. ”

Modification of the starting point:

From all available data on benzenesulfonic acid, di-C10 -14 -alkyl derivs., calcium salts, and on the calcium sulfonate read across substances for the different human health endpoints, it is clear that the substances exert their effects by a threshold mode of action. Thus, DNELs can be calculated for the different threshold endpoints based on the most relevant dose descriptors per endpoint. DNELs are derived based on the available toxicity data for the target substance and for the read across substances, reflecting the routes, the duration and the frequency of exposure. DNELs are derived for workers and the general population. The general population includes consumers and humans exposed via the environment.

Bioavailability (absorption):

There is no substance-specific experimental information on absorption by the oral, dermal and inhalation routes available. The absorption rates are assessed based on the physico-chemical properties and on the effects observed in treated animals in the available studies.

Oral absorption:

Due to the molecular weight of = 940 and = 1110 g/mol, a logPow of 6.91 together with LD50 of 10,000 mg/kg bw established in an oral acute toxicity study in rats and the very slight effects found at the highest dose level in the oral one-generation study in rats, absorption by oral route is considered to be slight to moderate for benzensulfonic acid, di-C10 -14 -alkyl dervis., calcium salts (for the detailed information on absorption please refer to section "Toxicokinetics, metabolism and distribution" of this CSR or section 7.1 of IUCLID file).The oral absorption is set to 50%since physico-chemical properties of the substance are not in range suggestive of significant absorption from the gastro-intestinal tract. The oral absorption is considered to be the same in animals and in humans (worst-case).

Dermal absorption:

No significant dermal absorption is expected for benzenesulfonic acid, di-C10 -14 -alkyl dervis., calcium salts. The log Pow of 6.91, the water solubility of < 0.1 mg/L and the molecular weight of = 940 and = 1110 g/mol point to apoor absorption through the skin.According to the TGD, Part I, Appendix IV, 10% of dermal absorption can be considered in this case, since the criteria for molecular weight and Log Pow are met (MW above 500 g/mol and log Pow > 4). Moreover, a critical assessment of all available data (toxicity effects in the available studies and physicochemical properties) should be taken into account before using default assumptions (ECETOC, TR No. 110). The absorption after dermal exposure is generally more gradual and slower than oral absorption and a lower bioavailability is expected due to the presence of the absorption hindering outer skin layer stratum corneum and a comparatively smaller surface area. Schuhmacher et al. recommended that a low dermal penetration (< 10%) can be assumed for substances with a logPow value >5 or for substances with a Kp value <0.0001 (cm/h). (Schumacher et al., 2003). A skin permeability constant (Kp) of 1.0E-7 cm/min (= 6.0E-6 cm/h) for human epidermis was obtained experimentally for the related substance dodecyl benzenesulfonate (CAS 25155-30-0, Howes, 1975). This substance is structurally similar to benzensulfonic acid, di-C10 -14 -alkyl dervis., calcium salts, but its alkyl chain consisting of 12 carbon atoms is shorter and therefore it is less lipophilic. The Kp value for benzenesulfonic acid, di-C10 -14 -alkyl dervis., calcium salts,which is even more lipophilic than dodecyl benzenesulfonate, is expected to be much lower. Thus, 10% absorption applies also in this case.

Dermal absorption in rats, rabbits and in humans is assumed to be the same since no information for dermal absorption of benzenesulfonic acid, di-C10 -14 -alkyl dervis., calcium salts in humans is available.

Reference:

1.Schuhmacher-Wolz U., Kalberlach F., Oppl R., van Hemmen J. J. (2003). A toolkit for dermal risk assessment: toxicological approach for hazard characterization. Ann. Occup. Hyg., Vol 47 No.8, pp. 641 -652.

Inhalation absorption

Absorption by inhalation is considered to be negligible (low vapour pressure of 0.01 Pa at 25°C) and not to be higher than absorption by oral route. Thus, 50% absorption is assumed for inhalation route and considered to be equal in rats and in humans since no substance specific information is available.

Route-to-route extrapolation:

Oral-to-inhalation extrapolation is performed to obtain long-term inhalation NOAEC for systemic effects. The following formula was used: corrected inhalatory NOAEC = oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (6.7 m³/10 m³) where sRV is standard respiratory volume of rats during 8 hours (= 0.38 m³/kg/day); ABS-absorption and 6.7 m³ and 10 m³ are standard respiratory volumes for workers under normal conditions and by light activity.

Exposure conditions:

No modification of the starting points for exposure conditions was necessary since the systemic dose after oral administration of the test material was already assessed in respiratory volume taken for rats during 8 h (0.38m³).

Differences in the respiratory volumes between experimental animals and humans were used when an oral rat NOAEL from the oral one-generation reproductive toxicity study in rats was used to assess inhalation exposure in humans. 0.38 m³/kg/day is the standard respiratory volumes in rats during 8h exposure. 6.7 and 10 m³ are standard respiratory volumes for workers under normal conditions and by light activity, respectively.

Applying of assessment factors and calculation of DNELs:

The assessment factors have been applied to the corrected starting point to obtain the endpoint specific DNELs. Assessment factors (AFs) correct uncertainties and variability within and between species in the effect data.

Interspecies differences:

The species-specific default assessment factor of 4 for allometric scaling for rats was applied in the case of employment of the oral NOAEL from the subchronic one-generation reproductive toxicity study, which was used to derive the dermal long-term DNEL.

No allometric scaling factor was applied when the oral NOAEL from the one-generation study was used for the derivation of inhalation long-term DNEL.

An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases.

An assessment factor of 1 was applied in case of DNEL calculation for skin sensitisation (local effects).

Intraspecies differences:

An assessment factor of 5 was applied for workers for all endpoints and for all exposure routes.

Extrapolation of duration:

An assessment factor of 2 was applied for duration of exposure (subchronic study). However, this is not applicable for sensitisation and therefore an assessment factor of 1 was applied.

Quality of whole data base:

A default assessment factor of 1 was used.

Issues related to dose response:

A default assessment factor of 1 was applied when the NOAEL from the oral one generation reproductive toxicity study was used.

Calculation of DNELs:

Acute/short-term exposure - local effects (dermal DNEL)

SCL descriptor:

Amount applied to skin = 0.2 mL x 0.9406 g/mL (density) x 10% (NOAEL/SCL concentration) = 0.0188 g = 18.8 mg

Amount applied per unit surface are = 18.8 mg / 3.63 cm² skin (based on 3/4 x 3/4 patch noted in a number of studies) = 5.18 mg/cm²

DNEL = 5.18 mg/cm² / (1 x 5 x 1 x 1 x 1) = 1.04 mg/cm².

Assessment factors are: 1 – interspecies, 5 – intraspecies, 1 – study duration (not applicable for sensitisation), 1 – dose response, 1 – quality of data base, 1 - NOAEL. The total AF amounts to 5.

Remarks: 0.2 mL is the standard volume applied in human patch tests.

Long-term exposure – systemic effects (dermal DNEL):

For the oral rat NOAEL of 500 mg/kg bw the following conversion was necessary:

dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS dermal-rat) x (ABS dermal-rat/ABS dermal-human) = 500 mg/kg bw x (50%/10%) = 2500 mg/kg bw

DNEL = 2500 mg/kg bw/(4 x 2.5 x 5 x 2 x 1 x 1) = 25 mg/kg bw.

Assessment factors are: 4 – interspecies, 2.5 – remaining interspecies differences, 5 – intraspecies, 2 – study duration (subchronic study), 1 – dose response, 1 – quality of data base. The total AF amounts to 100.

Long-term exposure – systemic effects (inhalation DNEL):

The oral rat NOAEL of 500 mg/kg bw was converted into the inhalation NOAEC:

Inhalation NOAEC = oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinhal-human) x (6.7 m³/10 m³) = 500 mg/kg bw x (1/0.38 m³/kg/day) x (50%/50%) x (6.7/10) = 881.58 mg/m³

DNEL = 881.58 mg/m³/(2.5 x 5 x 2 x 1 x 1) = 35.26 mg/m³.

Assessment factors are: 2.5 – remaining interspecies differences, 5 – intraspecies, 2 – study duration (subchronic study), 1 – dose response, 1 – quality of data base. The total AF amounts to 25.

Selected DNELs

DNEL (sensitisation)/ local dermal (acute(short-term) =1.04 mg/cm²

DNEL systemic dermal (long-term) =25 mg/kg bw

DNEL systemic inhalation =35.26 mg/m³

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 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:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:
The dose descriptor starting point is obtained by conversion of the oral NOAEL of 500 mg/kg bw from the oral one-generation toxicity study in rats with the calcium sulfonate read-across substance, (CAS 115733-09-0) (Bjorn, 2004) to an inhalation NOAEC taking into account an oral absorption of 50% and absorption by inhalation of 50%, the factor of 1/1.15 m³/kg/day for a 24 hour exposure.
AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
2
Justification:
since it is a subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scalling should be applied in case of oral-to-inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.5 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A NOAEL of 500 mg/kg bw /day from the one-generation oral repeated dose toxicity study with the calcium sulfonate read across substance, (CAS 115733-09-0), is available for rats (Bjorn, 2004). This value was converted into the corrected dermal NOAEL taking into account the rates for absorption (oral 50 %, dermal 10 %).
AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-4 fold)
AF for differences in duration of exposure:
2
Justification:
since it is a subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default factor for rats
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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:
DNEL (Derived No Effect Level)
Value:
0.518 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
other: NOAEL of 5.18 mg/cm²
AF for dose response relationship:
1
Justification:
Not applicable for sensitisation
AF for interspecies differences (allometric scaling):
1
Justification:
Deafult: no allometric scaling AF for local effects (skin sensitisation is a local effect)
AF for other interspecies differences:
1
Justification:
The DNEL is derived by using human data.
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
multiple reliable studies with Klimisch code 1 and 2
AF for remaining uncertainties:
1
Justification:
NOAEL to LOAEL

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):
200
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not relevant (oral route of exposure and oral study in rats).
AF for dose response relationship:
1
Justification:
default (three doses were tested, using a spacing range of 2-5 fold)
AF for differences in duration of exposure:
2
Justification:
since it is a subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default for rats
AF for other interspecies differences:
2.5
Justification:
default; no substance and route specific information on toxicokinetic and toxicodynamic is available for animals and humans
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
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

The principles of the DNEL calculation for the general population are the same as already described for workers. However, there are additional considerations or deviations for:

Modification of the starting point:

Bioavailability (absorption):

The oral absorption in rats and in humans is assumed to be the same since no information for oral absorption for benzenesulfonic acid, di-C10 -14 -alkyl derivs., calcium salts in rats and in humans is available.

Respiratory volumes:

No differences in the respiratory volumes under normal conditions and by light activity in humans were taken into account. A default respiratory volume of 1.15 m³/kg bw for rats was used to convert oral NOAEL into inhalation NOAEC.

Applying of assessment factors:

A higher assessment factor of 10 (in place of 5 for workers) for intraspecies variation/differences of human population was used.

Calculation of endpoint-specific DNEL for general population

Acute/short-term exposure - local effects (dermal DNEL)

SCL descriptor:

Amount applied to skin = 0.2 mL x 0.9406 g/mL (density) x 10% (NOAEL/SCL concentration) = 0.0188 g = 18.8 mg

Amount applied per unit surface are = 18.8 mg / 3.63 cm² skin (based on 3/4 x 3/4 patch noted in a number of studies) = 5.18 mg/cm²

DNEL = 5.18 mg/cm² / (1 x 10 x 1 x 1 x 1) = 0.518 mg/cm².

Assessment factors are: 1 – interspecies, 10 – intraspecies, 1 – study duration (not applicable for sensitisation), 1 – dose response, 1 – quality of data base, 1 - NOAEL. The total AF amounts to 10.

Remarks: 0.2 mL is the standard volume of applied volume in patch tests.

Long-term exposure - systemic effects (oral):

The oral NOAEL of 500 mg/kg bw had not to be converted.

The oral NOAEL of 500 mg/kg bw was not modified for differences in absorption by oral route since no substance- and route specific information is available: Oral NOAELrat= oral NOAELhuman= 500 mg/kg bw.

DNEL = 500 mg/kg bw/(4 x 2.5 x 10 x 2 x 1 x 1) = 2.5 mg/kg bw. Assessment factors are: 4 – interspecies, 2.5 – remaining interspecies differences, 10 – intraspecies, 2 – study duration, 1 – dose response (clear dose response), 1 – quality of data base (default). The total AF amounts to 200.

Long-term exposure - systemic effects (dermal):

For the oral rat NOAEL of 500 mg/kg bw the following conversion was necessary:

dermal NOAEL = oral NOAEL x (ABS oral-rat/ABS dermal-rat) x (ABS dermal-rat/ABS dermal-human) = 2500 mg/kg bw

DNEL = 2500 mg/kg bw/(4 x 2.5 x 10 x 2 x 1 x 1) = 12.5 mg/kg bw.

Assessment factors are: 4 – interspecies, 2.5 – remaining interspecies differences, 10 – intraspecies, 2 – study duration (subchronic study), 1 – dose response, 1 – quality of data base. The total AF amounts to 200.

Long-term exposure - systemic effects (inhalation):

The oral NOAEL of 500 mg/kg bw was converted into the inhalation NOAEC:

Corrected inhalation NOAEC = oral rat NOAEL x (1/1.15 m³/kg bw/day) x (ABSoral-rat/ABSinhal-human), where 1.15 is the standard respiratory volume (m³/kg bw) of rats during 24 h exposure, ABS is absorption (values are the same as described for workers).

Corrected Inhalation NOAEC = 500 mg/kg bw x (1/1.15 m³/kg/day) x (50%/50%) = 434.78 mg/m³

DNEL = 434.78 mg/m³/(2.5 x 10 x 2 x 1 x 1) = 8.70 mg/m³.

Assessment factors are: 2.5 – remaining interspecies differences, 10 – intraspecies, 2 – study duration, 1 – dose response (clear dose response), 1 – quality of data base (default). The total AF amounts to 50.

Selected DNELs

DNEL local dermal (short- term)/sensitisation = 0.518 mg/cm²

DNEL systemic oral =2.5 mg/kg bw

DNEL systemic dermal (long term) =12.5 mg/kg bw

DNEL systemic inhalation =8.70 mg/m³