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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 167 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Local effects

Reliable animal studies were available to assess the local effects of naphthalene-2-sulfonic acid. One mg of 80% naphthalene-2-sulfonic acid caused corrosion (full-thickness necrosis) on rabbit skin after 20 h exposure under occlusive conditions; strong irritant effects were seen after 15 min of exposure. Corrosive effects were also observed in an eye irritation study where 0.05 mL of naphthalene-2-sulfonic acid were instilled in the eyes of rabbits (BASF AG 1972). Therefore, a classification of R 34/ skin corrosion Cat. 1C is warranted for naphthalene-2 -sulfonic acid. However, a quantitative approach of an No-effect-level could not be made based on these studies. Due to low vapour pressure, no relevant exposure of the respiratory tract is expected.

 

Short-term exposure - systemic effects

There were no adverse systemic effects observed after short-term exposure. The mortalities seen in a acute toxicity study in rats after administration of 16% aqueous solution with naphthalene-2-sulfonic acid per gavage, leading to a LD50 of 1400 mg/kg bw (BASF AG 1972) are considered as consequence of local corrosive effects in the stomach as indicated by LD50 values above 5000 mg/kg bw with sodium salts of napthalene-1 -sulfonic acid and napthalene-2 -sulfonic acid. Therefore, a DNEL for short-term systemic effects is not warranted.

 

Long-term exposure - systemic effects

No relevant systemic toxic effects were observed in an extended one-generation study with the potassium salt of naphthalenesulfonic acids in rats. The test substance was applied for 15 weeks to parental rats in doses up to 1000 mg/kg bw/d. This value was therefore considered as lowest NOAEL for subchronic oral administration. This value was modified to get the correct starting point for the dermal and inhalative DNEL derivation.

For the oral-dermal extrapolation, a factor of 0.01 is used, based on the result of the ex vivo dermal absorption study with naphthalenesulfonic acid, sodium salt (Goldwell 1997). Here, 1% the test substance permeates through pig skin within 24 hours; the correct starting point was therefore 100,000 mg/kg bw/d. The low potential for dermal absorption is applicable only for intact skin. Regarding the corrosive effects of naphthalene-2 -sulfonic acid, it is considered that repeated dermal exposure to naphthalene-2-sulfonic acid leads to at least partial destruction of the skin tissue and, subsequently, to an increase of dermal absorption. However, this has to be considered as a secondary effect of the corrosive properties of naphthalene-2 -sulfonic acid; this hazard is assessed to be sufficiently covered by the qualitative assessment of the local effects.

 

Discussion of the applied assessment factors (for the dermal exposure; ECETOC 2003, 2010):

Remaining differences: 1

Interspecies factor: 4 (rat)

Intraspecies factor: 3 (worker)

Exposure duration: 2 (subchronic to chronic)

Dose response: 1

Data base quality: 1

Total assessment factor (AF) = 24

 

The DNEL for long-term dermal exposure, systemic effects is therefore considered to be (100,000/24 =) 4167 mg/kg bw/d.

 

For the oral-inhalation extrapolation, a default factor of 1 is used. Additionally, the DNEL was calculated by dividing the NOAEL of 1000 mg/kg bw/d with 0.38 m3/kg bw and then multiplying with 6.7 m3/ 10 m3 70 kg as described in the REACH guidance document R8 (2008; p.65) following the allometric scaling principle; the correct starting point was therefore 1763 mg/m3/d for the inhalative pathway.

 

Discussion of the applied assessment factors (for the inhalative exposure; ECETOC 2003, 2010):

Remaining differences: 1

Intraspecies factor: 3 (worker)

Exposure duration: 2 (subchronic to chronic)

Dose response: 1

Data base quality: 1

Total assessment factor (AF) = 6

 

The DNEL for long-term inhalative exposure, systemic effects is therefore considered to be (1763/6 =) 294 mg/m3/d.

 

However, the substance contains ca. 3.3% of naphthalene (CAS # 91-20-3). Therefore, as a worst-case assumption for repeated dose toxicity effects by inhalation of naphthalenesulfonic acids, the European long term limit value of naphthalene, 50 mg/m3/d, is considered as the most sensitive and most reliable DNEL for systemic effects after long-term inhalative exposure to workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
4.7
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 500 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral 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
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Local effects

See discussion above (DNEL for worker)

 

Short-term exposure - systemic effects

See discussion above (DNEL for worker)

 

Long-term exposure - systemic effects

For the origin of the basic NOAEL of 1000 mg/kg bw/d see discussion above (DNEL for worker). For consumer, following adoptions were made in contrast to the worker DNELs:

Additionally, a DNEL has to be determined for oral exposure.

 

Discussion of the applied assessment factors (for oral and dermal eposure pathways; ECETOC 2003, 2010):

Remaining differences: 1

Interspecies factor: 4 (rat)

Intraspecies factor: 5 (consumer)

Exposure duration: 2 (subchronic to chronic)

Dose response: 1

Data base quality: 1

Total assessment factor (AF) = 40

 

The DNEL for long-term dermal exposure, systemic effects is therefore considered to be (100,000/40=) 2500 mg/kg bw/d.

The DNEL for long-term oral exposure, systemic effects is therefore considered to be (1000/40=) 25 mg/kg bw/d.

 

Here, the inhalative DNEL was calculated by dividing the NOAEL of 1000 mg/kg bw/d with 1.15 m3/kg bw as described in the REACH guidance document R8 (2008; p.64) following the allometric scaling principle; the correct starting point was therefore 870 mg/m3/d for the inhalative pathway.

 

Discussion of the applied assessment factors (for the inhalative exposure; ECETOC 2003, 2010):

Remaining differences: 1

Intraspecies factor: 5 (consumer)

Exposure duration: 2 (subchronic to chronic)

Dose response: 1

Data base quality: 1

Total assessment factor (AF) = 10

 

The DNEL for long-term inhalative exposure, systemic effects is therefore considered to be (870/10=) 87 mg/m3/d.

 

However, the substance contains ca. 3.3% of naphthalene (CAS # 91-20-3) (see DNEL for worker). Therefore, as a worst-case assumption for repeated dose toxicity effects by inhalation of naphthalenesulfonic acids, based on the European long term limit value of naphthalene (50 mg/m3/d) following assessment factors were used to derive the DNEL for systemic effects after long-term inhalative exposure to the general population.

 

Discussion of the applied assessment factors (for the inhalative exposure; ECETOC 2003, 2010):

Remaining differences: 1

Intraspecies factor: 1.7 (worker to consumer)

Respiratory volume: 0.67 (10 m3/8 h to 6.7 m3/8 h)

Exposure duration: 4.2 (8 to 24 h, 5 to 7 d)

Dose response: 1

Data base quality: 1

Total assessment factor (AF) = 4.7

 

The DNEL for long-term inhalative exposure, systemic effects, based on repeated dose toxicity effects by inhalation

of naphthalene, is therefore considered to be (50/4.7=) 10.6 mg/m3/d. This is considered as most sensitive value and is therefore used to derive the most reliable DNEL for systemic effects after long-term inhalative exposure to the general population.

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