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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
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.58 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation was used as it is no lung absorption information to estimate the systemic dose from the air concentration, then the oral NOAEL was used as starting point. The dose descriptor starting point of 881 mg/m3 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:
A default assessment factor of 1 was applied when the NOAEL from the oral one generation reproductive toxicity study was used
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 was applied for duration of exposure (subchronic study).
AF for interspecies differences (allometric scaling):
1
Justification:
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.
AF for other interspecies differences:
2.5
Justification:
An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases.
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 was applied for workers
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
No addiitonal uncertainties were considered
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
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation was used as it is no dermal absorption information to estimate the systemic dose from the dermal dose, then the oral NOAEL was used as 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 a dermal NOAEL taking into account an oral absorption of 50 % and dermal absorption of 10%. Thereby the corrected starting dermal NOAEL is: oral NOAEL * (ABS oral-rat/ABS dermal-rat) * (ABS dermal-rat/ABS dermal-human) = 2500 mg/kg bw

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 was applied when the NOAEL from the oral one generation reproductive toxicity study was used
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 was applied for duration of exposure (subchronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
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.
AF for other interspecies differences:
2.5
Justification:
An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 was applied for workers
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.1 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
An assessment factor of 1 was applied in case of DNEL calculation for skin sensitisation
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 was applied
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor of 1 was applied
AF for other interspecies differences:
1
Justification:
An assessment factor of 1 was applied in case of DNEL calculation for skin sensitisation
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 was applied for workers
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
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:
no hazard identified

Additional information - workers

Modification of the starting point:

From all available data on benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts, and on the respective 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 ca. 500 -530 g/mol, a logPow of 8.8 together with LD50 of >5,000 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 benzenesulfonic acid, di-C10-14-alkyl derivs., sodium 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 derivs., sodium salts. The logPow of 8.8, the water solubility of < 0.1 mg/L and the molecular weight of ca. 500 -530 g/mol point to a poor absorption through the skin. 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 benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts. 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 derivs., sodium 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 (due to a very low vapour pressure) 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. In rats, 0.38 m³/kg/day is the standard 8-hr respiratory volume, whereas for workers the standard respiratory volume for workers are 6.7 and 10 m³ under normal conditions and by light activity, respectively.

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
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation was used as it is no lung absorption information to estimate the systemic dose from the air concentration, then the oral NOAEL was used as starting point. 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

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 was applied when the NOAEL from the oral one generation reproductive toxicity study was used.
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 was applied for duration of exposure (subchronic study).
AF for interspecies differences (allometric scaling):
1
Justification:
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
AF for other interspecies differences:
2.5
Justification:
An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation was used as it is no dermal absorption information to estimate the systemic dose from the dermal dose, then the oral NOAEL was used as starting point. 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.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 was applied when the NOAEL from the oral one generation reproductive toxicity study was used.
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 was applied for duration of exposure (subchronic study).
AF for interspecies differences (allometric scaling):
4
Justification:
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
AF for other interspecies differences:
2.5
Justification:
An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases.
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.55 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
An assessment factor of 1 was applied in case of DNEL calculation for skin sensitisation
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 was applied
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor of 1 was applied
AF for other interspecies differences:
1
Justification:
An assessment factor of 1 was applied in case of DNEL calculation for skin sensitisation (local effects).
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
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:
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
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

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.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 was applied when the NOAEL from the oral one generation reproductive toxicity study was used.
AF for differences in duration of exposure:
2
Justification:
An assessment factor of 2 was applied for duration of exposure (subchronic study).
AF for interspecies differences (allometric scaling):
4
Justification:
Default for rats
AF for other interspecies differences:
2.5
Justification:
An assessment factor of 2.5 was applied for remaining interspecies differences in toxicodynamics between rat and human in all cases
AF for intraspecies differences:
10
Justification:
Default for general population
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 was used
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

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., sodium 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.