Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral: rat male/female LD50 = ca.1800 mg/kg  (BASF, 1970) ; rat male LD50 = 1790 mg/kg (Bayer, 1971); mouse male LD50 = 3300 mg/kg (Bayer, 1971 ; equivalent to a rat LD50 of 1886 mg/kg taking into account allometric scaling for interspecies extrapolation)
Acute toxicity, inhalation: LC50 male/female rat (aerosol, 4h) = 4.08 mg/L (BASF, 1987)
Acute toxicity, dermal: rabbit male/female LD50 = ca. 3000 mg/kg (BASF, 1970)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is sufficiently documented. Basic data given: comparable to guidelines/standards. Test substance purity is 65%.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gassner/Ottobrunn, Germany
- Weight at study initiation: mean: male = 225 g, female = 165 g
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
other: aqueous solution with traganth
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4, 8, 16, 20, 30%

Doses:
3200, 2500, 2000, 1600, 800, 400 mg/kg bw
No. of animals per sex per dose:
10; except for the 1600 mg/kg bw dose group (20 animals per sex)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
Statistics:
no data available
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
ca. 1 800 mg/kg bw
Based on:
test mat.
Remarks:
(equivalent to the substance as registered)
Mortality:
3200 mg/kg bw: all animals died within 24 hours
2500 mg/kg bw: 9/10 males and all females died within 24 hours
2000 mg/kg bw: 5/10 males died (4 within 48 hours, 1 between 7 and 14 days); 7/10 females died within 24 hours, one more after 48 h and by day 14 all females were dead
1600 mg/kg bw: 0/20 males died; 11/20 females were dead after 24 hours, 12/20 after 48 hours and 13/20 after 7 days
800 and 400 mg/kg bw: all animals survived
Clinical signs:
3200 mg/kg bw: dyspnea, partly diarrhea
remaining dose groups: dyspnea, dislike to move, calm behavior after administration of high doses (2500 and 1600 mg/kg bw, respectively) partly abdominal position, bloody snout and paw; surviving animals after 6 to 13 days without abnormal symptoms.
Body weight:
no data available
Gross pathology:
found dead: smeared anus (result of diarrhea), ectasia of stomach which contained a lot liquid, loose intestinal tract, slightly serous blurred snouts
sacrificed scheduled: nothing abnormal detected
Other findings:
no data available

Table: results

Doses

mg/kg

Concentration in vehicle

%

N° of animals

mortality

1 hour

24 hours

48 hours

7 days

14 days

3200

30

10 males

10 females

0/10

0/10

10/10

10/10

10/10

10/10

10/10

10/10

10/10

10/10

2500

20

10 males

10 females

0/10

0/10

9/10

10/10

9/10

10/10

9/10

10/10

9/10

10/10

2000

20

10 males

10 females

0/10

0/10

0/10

7/10

4/10

9/10

4/10

10/10

5/10

10/10

1600

16

20 males

20 females

0/20

0/20

0/20

11/20

0/20

12/20

0/20

13/20

0/20

13/20

800

8

10 males

10 females

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

400

4

10 males

10 females

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the oral LD50 of Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda was ca. 1800 mg/kg in rats.
Executive summary:

In an acute oral toxicity study (similar to OECD TG 401; 1970), groups of Sprague Dawley rats (10 or 20/sex) were given a single oral dose of the test substance in an aqueous solution with traganth at 3200, 2500, 2000, 1600, 800 and 400 mg/kg bw and observed for 14 days. Mortality occurred from the 1600 mg/kg bw dose group onwards. Dyspnea and diarrhea were seen, being common symptoms in acute tests. Surviving animals recovered after 6 to 13 days. At autopsy, liquid filled stomachs and loose intestinal tracts were found. No deviations from normal morphology were found in the animals which were scheduled sacrificed. An approximated LD50 of ca. 1800 mg/kg bw was estimated.

As the acute oral LD50 was ca. 1800 mg/kg under the conditions of the test, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is classified as Acute tox. 4 (H302) according to the Regulation (EC) 1272/2008 (CLP) and as harmful Xn, R22 according the Directive 67/548/CEE.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 800 mg/kg bw
Quality of whole database:
Three studies are available for the acute oral toxicity endpoint and are of good reliability (Klimisch score = 2)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is sufficiently documented. Guideline study (OECD); test substance purity ca. 70%.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: about 8 - 9 weeks
- Weight at study initiation: mean: male = 256 ± 22.2 g; female = 182 ± 15.0 g
- Housing: 5 females/cage and 1 male/cage
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
other: dust aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-Nose-Inhalationsystem INA20 (BASF SE)
- Exposure chamber volume: 55 L
- Method of holding animals in test chamber: animals were sitting in a tube
- Rate of air: 1500 L/h
- System of generating particulates/aerosols: Vibrationdispenser for highest dose group and a Brushdispenser for the two other groups

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: respirable dust: 87%, 77%, 77% for low, mid and high dose group
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
1.09 mg/L dose group: MMAD 50% = 3.4 µm / GSD = 2.8
3.49 mg/L dose group: MMAD 50% = 4.5 µm / GSD = 3.2
4.76 mg/L dose group: MMAD 50% = 4.0 µm / GSD = 3.6
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1.09, 3.49 and 4.76 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days or 28 days
- Frequency of observations and weighing: Weighing occured on day 7 and on day 14 or on days 7, 14 and 28. Observations were done daily on working days.
- Necropsy of survivors performed: yes
Statistics:
Probit analysis
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.08 mg/L air (analytical)
Based on:
test mat.
Remarks:
(equivalent to the substance as registered)
95% CL:
3.64 - 4.56
Exp. duration:
4 h
Mortality:
4.76 mg/L: 4/5 males and 5/5 females died within 24 hours
3.49 mg/L: 1/5 males died after 14 days, 2/5 females died after 21 days
1.09 mg/L: no animal died
Clinical signs:
other: during exposition: slight attempt to escape, clear discharge from nose, salivation additionally for groups 4.76 and 3.49 mg/L: accelerated respiration, eyelid closure, irregular and intermittent respiration, reddish discharge from nose after exposition:
Body weight:
Normal body weight gain was seen in lowest dose group. The mid dose group showed reduced body weight gain in the first week after exposure. In the second week they gained weight normally.
Gross pathology:
deceased animals: mid dose group: excessive loss of weight, stomach/intestines empty, filled with gas
high dose group: general congestive hyperemia, lung was filled with blood and edema
sacrificed animals: organs without abnormal detection
Other findings:
no data available

The LC50 value after the 28-day observation period was estimated at 3.82 mg/L.

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda induced acute toxicity after a single exposure of rat by inhalation (aerosol, 4h). As the LC 50 in males and females is comprised between 1.0 and 5.0 mg/L air, the registered substance is considered as harmful by inhalation and is therefore classified as Acute tox. 4 (H332) according to the Regulation (EC) 1272/2008 and as Xn, R20 according to the Directive 67/548/EEC.
Executive summary:

In an acute inhalation toxicity study according to OECD Guideline 403 (1987), groups of young adult Wistar rats (5/sex) were exposed by inhalation route to the test substance as dust aerosol for 4 hours to head/nose only at concentrations of 1.09, 3.49, or 4.76 mg/L. Animals then were observed for up to 28 days. Deaths did not occur in the low exposure concentration. At the mid dose group one male died on test day 14 (20% mortality) and two females on test day 21 (40%). One male animal survived the exposure with 4.76 mg/L test substance. The mean body weight gain was reduced in the mid dose group in the first week whereas in the second week it was normal again. The low dose group showed normal body weight gain. Slight attempt to escape, clear discharge from nose, salivation were symptoms seen during exposure in any dose group. In the mid and high dose group also following symptoms were seen: accelerated respiration, eyelid closure, irregular and intermittent respiration, reddish discharge from nose. After exposure, bloody smeared snout, salivation, piloerection were noted in animals of the low dose group on the first day after exposure. Bloody discharge from nose, reddish head, accelerated respiration, piloerection, anogenital region smeared with urine, respiratory sounds, reduced general state, reduced defecation, partly expanded abdomen and anemic aspect, high stepping gait, intermittent respiration were noted in animals of the mid dose group. These symptoms were seen until the end of observation. Partly accelerated respiration, blood smeared head, reddish discharge from nose, fur in thorax region reddish soiled, slight reduced general state, piloerection was found in one male from the high dose group. The animal was without symptoms on day 7 after exposure. At necropsy dead animals from high dose group showed general congestive hyperemia and a lung filled with blood and edema. The animals which died from the mid dose group showed excessive loss of weight, empty stomach/intestines, filled with gas. Sacrificed animals showed no abnormal detection at gross pathology.

As derived from the overall study results the acute LC50 values for a 14 -day observation period are: 

LC50 = 4.08 mg/L (95% C.I. 3.64 - 4.56) based on test substance (ca. 70% sodium diisobutylnaphthalenesulphonate).

Under the test conditions, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda induced acute toxicity after a single exposure of rat by inhalation (aerosol, 4h). As the LC 50 in males and females is comprised between 1.0 and 5.0 mg/L air, the registered substance is considered as harmful by inhalation and is therefore classified as Acute tox. 4 (H332) according to the Regulation (EC) 1272/2008 and as Xn, R20 according to the Directive 67/548/EEC.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
4 080 mg/m³
Quality of whole database:
not GLP study but conducted according to OECD guideline no. 403 (Klimish score = 2)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is sufficiently documented. Basic data given: comparable to guidelines/standards. Test substance purity is 65%.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BASF
- Weight at study initiation: mean: male and female = 2.4 kg
- Diet: ad libitum
- Water: ad libitum
Type of coverage:
not specified
Vehicle:
water
Details on dermal exposure:
The product was administered in various dosages as a 50% aqueous dispersion processes once to the shaved skin.
Duration of exposure:
24 hours
Doses:
1000, 2000, 4000 mg/kg bw
No. of animals per sex per dose:
4000 mg/kg: 4 males and 2 females; 2000 mg/kg: 1 male and 2 females; 1000 mg/kg: 2 males and 1 female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
Statistics:
no data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 3 000 mg/kg bw
Based on:
test mat.
Remarks:
(equivalent to the substance as registered)
Mortality:
4000 mg/kg: 3 males and 1 female died between 48 hours and day 14.
2000 and 1000 mg/kg: all animals survived
Clinical signs:
4000 mg/kg: Apathy, weight loss, reduced food intake were observed. No clinical signs in the surviving animals after 3-4 days.
2000 and 1000 mg/kg: No clinical signs observed.
Body weight:
no data available
Gross pathology:
Deceased animal: Petechiae on the mucous membranes of the stomach in 3/4 rabbits at 4000 mg/kg.
Other findings:
no data available

Table: results

Doses

mg/kg

Concentration

%

N° of animals

mortality

1 hour

24 hours

48 hours

7 days

14 days

4000

50

4 males

2 females

0/4

0/2

0/4

0/2

2/4

1/2

3/4

1/2

3/4

1/2

2000

50

1 male

2 females

0/1

0/2

0/1

0/2

0/1

0/2

0/1

0/2

0/1

0/2

1000

50

2 males

1 female

0/2

0/1

0/2

0/1

0/2

0/1

0/2

0/1

0/2

0/1

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda was ca. 3000 mg/kg in rabbits.
Executive summary:

The substance has been tested for acute dermal toxicity in rabbits, according to a method similar to O.E.C.D. guideline Nb.402. The test article was applied as a 50% aqueous dispersion to groups of male and female rabbits at doses of 1000, 2000 and 4000 mg/kg bw, respectively for 24 hours. At the end of the period of exposure, the animals were examined for 14 days.

At 4000 mg/kg, 3 males and 1 female died between 48 hours and day 14. Apathy, weight loss, reduced food intake were observed. No clinical signs were observed in the surviving animals after 3-4 days. At 2000 and 1000 mg/kg, all animals survived. No clinical signs were observed.

As the acute dermal LD50 was calculated as ca. 3000 mg/kg under the conditions of the test, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is not classified according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/CEE.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw
Quality of whole database:
Study performed similarly to the OECD 402 Guideline (Klimisch score = 2)

Additional information

Acute oral toxicity:

Two Klimisch score 2 rat studies were available for oral route. One study was used as a key study and the other one used as supporting:

In the key study, groups of Sprague Dawley rats (10 or 20/sex) were given a single oral dose of the test substance in an aqueous solution with traganth at 3200, 2500, 2000, 1600, 800 and 400 mg/kg bw and observed for 14 days. Mortality occurred from the 1600 mg/kg bw dose group onwards. Dyspnea and diarrhea were seen, being common symptoms in acute tests. Surviving animals recovered after 6 to 13 days. At autopsy, liquid filled stomachs and loose intestinal tracts were found. No deviations from normal morphology were found in the animals which were scheduled sacrificed. A LD50 of ca. 1800 mg/kg bw was estimated. As the acute oral LD50 was ca. 1800 mg/kg under the conditions of the test, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic sodais classified as Acute tox. 4 (H302) according to the Regulation (EC) 1272/2008 (CLP) and as harmful Xn, R22 according the Directive 67/548/CEE.

In the supporting study, the substance has been tested for acute oral toxicity in Male rats. The test article was administered as an aqueous solution to groups of male Wistar rats at doses of 500, 1000, 1500, 1750, 1850, 2000 and 2250 mg/kg bw (active ingredient), respectively. Death occured within 1 to 3 days at 1750, 1850, 2000 and 2250 mg/kg. The signs of intoxication (deterioration of general health, labored breathing) occured within 2 hours at 1000, 1500, 1750, 1850, 2000 and 2250 mg/kg. These signs could be observed from 2 to 3 days. Acute oral LD50 was calculated as 1790 mg/kg in terms of active ingredient under the conditions of the test.

One Klimisch score 2 mouse study was available for oral route and was selected as supporting study:

The substance sodium diisobutylnaphtalene sulfonate has been tested for acute oral toxicity in Male NMRI mice. The test article was administered as an aqueous solution to groups of male NMRI mice at doses of 500, 1000, 1500, 2500, 3000, 3500, 4000, 4500 and 5000 mg/kg bw (active ingredient), respectively. Death occured within 1 to 2 days at 2500, 3000, 3500, 4000, 4500 and 5000 mg/kg. The signs of intoxication (deterioration of general health, labored breathing) were observed at 2500, 3000, 3500, 4000, 4500 and 5000 mg/kg. These signs could be observed from 3 to 7 days. Acute oral LD50 was calculated as 3300 mg/kg in terms of active ingredient under the conditions of the test. When taking into account the allometric scaling for interspecies extrapolation (see Table R.8-3 in ECHA Guidance on information requirements and chemical safety assessment, Allometric Scaling factor = 4 in rat and 7 in Mouse), this dose of 3300 mg/kg in mice is equivalent to 1186 mg/kg bw in rat (3300*4/7), which is consistent with the LD 50 values obtained in the above mentioned rat studies.

Acute inhalation toxicity:

One Klimisch score 2 study was available for inhalation route and was used as a key study:

In an acute inhalation toxicity study conducted according to OECD Guideline 403 (1987), groups of young adult Wistar rats (5/sex) were exposed by inhalation route to the test substance as dust aerosol for 4 hours to head/nose only at concentrations of 1.09, 3.49, or 4.76 mg/L. Animals then were observed for up to 28 days. Deaths did not occur in the low exposure concentration. At the mid dose group one male died on test day 14 (20% mortality) and two females on test day 21 (40%). One male animal survived the exposure with 4.76 mg/L test substance. The mean body weight gain was reduced in the mid dose group in the first week whereas in the second week it was normal again. The low dose group showed normal body weight gain. Slight attempt to escape, clear discharge from nose, salivation were symptoms seen during exposure in any dose group. In the mid and high dose group also following symptoms were seen: accelerated respiration, eyelid closure, irregular and intermittent respiration, reddish discharge from nose. After exposure, bloody smeared snout, salivation, piloerection were noted in animals of the low dose group on the first day after exposure. Bloody discharge from nose, reddish head, accelerated respiration, piloerection, anogenital region smeared with urine, respiratory sounds, reduced general state, reduced defecation, partly expanded abdomen and anemic aspect, high stepping gait, intermittent respiration were noted in animals of the mid dose group. These symptoms were seen until the end of observation. Partly accelerated respiration, blood smeared head, reddish discharge from nose, fur in thorax region reddish soiled, slight reduced general state, piloerection was found at the one male from the high dose group. The animal was without symptoms on day 7 after exposure. At necropsy dead animals from high dose group showed general congestive hyperemia and a lung filled with blood and edema. The animals which died from the mid dose group showed excessive loss of weight, empty stomach/intestines, filled with gas. Sacrificed animals showed no abnormal detection at gross pathology.

As derived from the overall study results the acute LC50 values for a 14 -day observation period are: 

LC50 = 4.08 mg/L (95% C.I. 3.64 - 4.56) based on test substance (ca. 70% sodium diisobutylnaphthalenesulphonate).

Under the test conditions, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda induced acute toxicity after a single exposure of rat by inhalation (aerosol, 4h). As the LC 50 in males and females is comprised between 1.0 and 5.0 mg/L air, the registered substance is considered as harmful by inhalation and is therefore classified as Acute tox. 4 (H332) according to the Regulation (EC) 1272/2008 and as Xn, R20 according to the Directive 67/548/EEC.

Acute dermal toxicity:

One Klimisch score 2 study was available for dermal route and was used as a key study:

The substance has been tested for acute dermal toxicity in rabbits, according to a method similar to O.E.C.D. guideline Nb.402. The test article was applied as a 50% aqueous dispersion to groups of male and female rabbits at doses of 1000, 2000 and 4000 mg/kg bw, respectively for 24 hours. At the end of the period of exposure, the animals were examined for 14 days.

At 4000 mg/kg, 3 males and 1 female died between 48 hours and day 14. Apathy, weight loss, reduced food intake were observed. No clinical signs were observed in the surviving animals after 3-4 days. At 2000 and 1000 mg/kg, all animals survived. No clinical signs were observed.

As the acute dermal LD50 was calculated as ca. 3000 mg/kg under the conditions of the test, Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is not classified according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/CEE.


Justification for selection of acute toxicity – oral endpoint
The selected study was determined as the key study for the registration dossier as this study was of good reliability (Kr.2), was performed according to a method equivalent to OECD test guideline and was performed on males and females rats unlike the other study (1971) which was thus assigned as supporting study.

Justification for selection of acute toxicity – inhalation endpoint
only one study available (not GLP but OECD guideline 403 compliant)

Justification for selection of acute toxicity – dermal endpoint
Only one study available (similar to OECD guideline 402).

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008 including ATP3.

Self classification:

Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is classified for acute oral toxicity as Acute tox.4, H302 ( Harmful if swallowed) according to the Regulation (EC) 1272/2008 (CLP) and Xn, R22 (Harmful if swallowed) according to the Directive 67/548/EEC as the oral LD50 (rat) is 1800 mg/kg.

Reaction product of naphthalene, butanol, sulfonated and neutralized by caustic soda is also classified for acute inhalation toxicity as Acute tox.4, H332 (Harmful if inhaled) according to the Regulation (EC) 1272/2008 (CLP) and Xn, R20 (Harmful by inhalation) according to the Directive 67/548/EEC as the LC50 male/female rat (aerosol, 4h) is 4.08 mg/L.