Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda

Endpoint summary

Description of key information

Acute toxicity, oral: rat male/female LD50 = between 600 and 1800 mg/kg  (Corroller, 1994) ; rat male LD50 = approx.  1350 mg/kg) (Shaffer, 1957)
Acute toxicity, inhalation: LC50 male rat (aerosol, 4h) = 1.09 mg/L; LC50 female rat (aerosol, 4h) = 2.93 mg/L  (Nagy, 2013)
Acute toxicity, dermal: rabbit male LD50 = approx. 4200 mg/kg  (Shaffer, 1957)

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:

From 05 August 1997 to 10 October 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed according to EU / OECD guidelines and non- GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Credo, 69210 L'Arbresle. France.
- Age at study initiation: 6 weeks old
- Weight at study initiation: 177-206 g for the males, 162-186 g for the females
- Fasting period before study: Animals are fasted the day before. They are divided into 3 groups of 10 (five of each sex).
- Housing: The animals were housed in groups of 5 animals of the same sex in polypropylene cages (310x465x190).
- Food consumption (e.g. ad libitum): ad libitum. Pelleted feed UAR A04-10 (91360 - EPINAY SUR ORGE, FRANCE)
- Water consumption (e.g. ad libitum): ad libitum
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data available
- Humidity (%): no data available
- Air changes (per hr): no data available
- Photoperiod (hrs dark / hrs light): no data available

In-life dates: From 05 to 28 August 1997

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
The vehicle used was distilled water (Meram lot 62421)

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg


DOSAGE PREPARATION:
The test substance is used diluted in distilled water. It is maintained under magnetic stirring for the duration of treatment.

Doses:

200, 600 and 1800 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

DETAILS ON STUDY DESIGN
- Duration of observation period following administration: 14 days
- Frequency of observations: the animals were observed frequently after administration of the test substance and at least once a day for clinical signs and at least twice a day for mortality.
- Frequency of weighing: Animals were weighed just before administration of the test substance and then on days 4, 8 and 15.
- Necropsy of survivors performed: yes on day 15
- Other examinations performed: macroscopic examination at necropsy (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities)

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 600 - < 1 800 mg/kg bw

Based on:

test mat.

Mortality:

At 200 and 600 mg/kg, no deaths occured during the observation period.
At 1800 mg/kg, one female died after 5 h, 2 males and 3 females died on day 2.

Clinical signs:

other: No clinical signs were observed during the study in animals treated with 200 and 600 mg/kg. Piloerection, decreased motor activity, hypertension and loss of grip were noted in animals treated with 1800 mg/kg at least until the 6th hour of observation. Dur

Gross pathology:

The macroscopic examination of the main organs of the animals death during the test or sacrified at the end of the study revealed no apparent abnormalities.

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 the test item reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda was between 600 and 1800 mg/kg in rats.

Executive summary:

The substance reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda has been tested for acute oral toxicity in Sprague Dawley rats, according to O.E.C.D. guideline Nb.401. The test article (76% active), diluted in distilled water, was administered as a single dose of 200, 600 and 1800 mg/kg bw to groups of 5 males and 5 females, at a dosing volume of 5 ml/kg. Following treatment, mortality, clinical signs and body weight were recorded for a two-week observation period. On day 15, the animals were euthanatized and necropsied.

 

At 200 and 600 mg/kg, no deaths occured during the observation period. At 1800 mg/kg, one female died after 5 h, 2 males and 3 females died on day 2. 

No clinical signs were observed during the study in animals treated with 200 and 600 mg/kg. Piloerection, decreased motor activity, hypertension and loss of grip were noted in animals treated with 1800 mg/kg at least until the 6th hour of observation. During the daily examinations performed during the observation period day 2 to day 15, no impairment of general condition and behavior of surviving animals were noted.

The body weight gain of the animals was normal in animals treated with 200 and 600 mg/kg. The body weight gain of the surviving males treated with 1800 mg/kg on day 15 was slightly lower (-14%) than other doses, but their weight change was however satisfactory. The surviving female treated with 1800 mg/kg presented a slight weight loss at day 4. This weight drop was offset later, his weight gain appeared normal and satisfactory at the end of the observation.

The macroscopic examination of the main organs of the animals dead during the test or sacrified at the end of the study revealed no apparent abnormalities.

 

As the acute oral LD50 was found between 600 and 1800 mg/kg (456 -1368 mg/kg as active) under the conditions of the test, reaction product of naphthalene, propan-2-ol, 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 to the Directive 67/548/CEE.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

600 mg/kg bw

Quality of whole database:

Two studies are available for the acute oral toxicity endpoint and are of good reliability (Klimisch score = 2). Furthermore, the results obtained in both studies are consistent, so that the whole dataset is considered of good quality.

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:

From 28 September 2012 to 22 January 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

The humidity was not measured during animal exposures. The temperature value occasionally deviated from the required range and was >25ºC during the animal exposure in Group 1-3 (23.2 to 26.5ºC) These deviations had no impact on the outcome of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

yes

Remarks:

The humidity was not measured during animal exposures. The temperature value occasionally deviated from the required range and was >25ºC during the animal exposure in Group 1-3 (23.2 to 26.5ºC) These deviations had no impact on the outcome of the study.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

yes

Remarks:

The humidity was not measured during animal exposures. The temperature value occasionally deviated from the required range and was >25ºC during the animal exposure in Group 1-3 (23.2 to 26.5ºC) These deviations had no impact on the outcome of the study.

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: 216 to 446 g (males: 358-446g; females: 216-262g)
- Fasting period before study: no
- Housing: Group of 5 (by sex) or 2 in case of sighting group in type III solid floor cages with stainless steel mesh lids. Lignocel Bedding for Laboratory Animals was available to animals during the study. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet (e.g. ad libitum): ssniff SM R/M-Z+H “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest Germany), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 – 70 %
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: From 17 October 2012 to 28 November 2012

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The animals were exposed to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises of two, concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers. Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports.
- Exposure chamber volume: 3.85 L
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: The flow of air through each port was at least, approximately, 0.7 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it approximately double the respiratory minute volume of a rat.
- Method of conditioning air: no data
- System of generating particulates/aerosols: Due to the granular nature of the material, suitable test atmospheres could not be produced from the material as supplied. Prior to use the test item was ground using a Ball Mill - "Mixer Mill MM 400" (Production number: 129050216). The test item was aerosolised using a Wright’s Dust Feed System (TSE Systems GmbH, Bad Homburg, Germany) located at the top of the exposure chamber. Compressed air was supplied by means of an oil-free compressor and passed through a suitable filter system prior to introduction to the dust generator.
- Method of particle size determination: The particle size of the test atmosphere was determined three times during the exposure period using a 7-stage impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany).
- Treatment of exhaust air: After passing through the animal’s breathing zone, spent aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic.
- Temperature, humidity, pressure in air chamber: see Table 7.2.2/1

TEST ATMOSPHERE
- Brief description of analytical method used: Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone) by pulling a suitable, known volume of test atmosphere through weighed GF10 glass fibre filters (Whatman GmbH, Hahnestraße 3 – D-37586 Dassel, Germany). The difference in the pre- and post-sampling weights, divided by the volume of atmosphere sampled, was equal to the actual achieved test atmosphere concentration. The nominal concentration was calculated by dividing the mass of test material disseminated into the chamber by the total volume of air that went through the chamber during the same period. This data was used to monitor the effectiveness of the test item atomization (between 10 and 90% depending on the nature of the test item).
- Samples taken from breathing zone: yes

VEHICLE
not applicable

TEST ATMOSPHERE (if not tabulated)
see Table 7.2.2./1

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: In the lack of any preliminary toxicological information, 5 mg/L was selected to be the starting target dose in the sighting study, in accordance with the OECD Test Guideline No. 403 recommendations.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see Table 7.2.2./1

Duration of exposure:

4 h

Concentrations:

Sighting study (Group 0.1)= 5.07 mg/L
Main study (Groups 1-4) = 1.04; 2.52; 0.51 and 5.14 mg/L

No. of animals per sex per dose:

Sighting study: 2/sex
Main study: 5/sex in groups 1 and 2; 5 males in group 3; 5 females in group 4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were checked five times on day of exposure and twice daily (early and late in the working day) during the observation period for morbidity and/or mortality. All animals were observed for clinical signs at hourly intervals during exposure, as soon as practicable following removal from restraint at the end of exposure, one hour after exposure and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: during necropsy, detailed examination of the abdominal and thoracic cavities. Special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity.

Statistics:

The four-hour LC50 values were calculated using SPSS software and a log/probit method

Preliminary study:

Two males and 2 females were treated at a target dose level of 5 mg/L (Group No. 0.1). Mortality was observed in both males and in 1/2 females. Laboured respiration was recorded for all animals during the exposure. Three animals died during the first two hour of the exposure. For last survivor, noisy respiration, sneezing, ataxia, hunched posture and weak condition were recorded shortly after the exposure and several days after exposure. No clinical signs were noted from Day 7. Therefore 1 mg/L was chosen as starting dose for the main study.

Sex:

male

Dose descriptor:

LC50

Effect level:

1.09 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: mortality and macroscopic findings, mainly in the lungs and trachea, recorded from the dose of 1.04 mg/L

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 2.93 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: mortality and macroscopic findings, mainly in the lungs and trachea, recorded from the dose of 2.52 mg/L

Mortality:

Premature death was recorded in 3/4 animals dosed at 5.07 mg/L during the sighting exposure and in 2/10, 6/10 and 5/5 rats at dose levels of 1.04, 2.52 and 5.14 mg/L, respectively in the main study. No mortality was reported at 0.51 mg/L. The death ocurred almost in all cases during the exposure period. See details in Table 7.2.2/2

Clinical signs:

other: The following test item-related clinical signs were recorded during the course of the study: laboured, gasping and/or noisy respiration, respiratory rate increased, sneezing, decreased activity, ataxia, hunched posture, weak and/or wasted condition. Mainl

Body weight:

Normal bodyweight gain was noted for the surviving animals during the observation period in all groups, with the exception of Group 1 (1.04 mg/L) where slight bodyweight loss was recorded in two males during the first three days.

Gross pathology:

At 5.07 and 5.14 mg/L, dark/red discoloration of the non-collapsed lungs and white foamy material in the trachea were seen in all found dead animals (n=8). These findings were associated with enlargement and red discoloration of the liver in five of them and presence of clear/beige liquid at the fur of head or of the perinasal area in four of them. No macroscopic findings were seen in the surviving female.
At 2.52 mg/L and 1.04 mg/L, similar findings were recorded in the lungs, trachea and fur of all found dead animals. No macroscopic findings were seen in the surviving animals.
At 0.51 mg/L, no macroscopic findings were seen in any animals

Other findings:

no other findings

Table 7.2.2/2: Mortality rates

Group Number	Mean Achieved Concentration (mg/L)	Male Deaths	Female Deaths	Total Deaths
0.1	5.07	2/2	1/2	3/4
1	1.04	2/5	0/5	2/10
2	2.52	5/5	1/5	6/10
3	0.51	0/5	-	0/5
4	5.14	-	5/5	5/5

 

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, propan-2-ol, 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, performed according to OECD Guideline 403 and in compliance with the GLP, groups of Wistar rats (2/sex in the sighting study and 5/sex in the main study) were exposed by inhalation route to aerosol of Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda (powder) for 4 hours at achieved concentrations of 5.07 (sighting study); 0.51, 1.04, 2.52 and 5.14 mg/L (main study).  Animals then were observed for 14 days for mortality, clinical signs and bodyweight gain and then euthanized for gross necropsy.

 

Premature death was recorded in 3/4 animals dosed at 5.07 mg/L during the sighting exposure and in 2/10, 6/10 and 5/5 rats at dose levels of 1.04, 2.52 and 5.14 mg/L, respectively in the main study. No mortality was reported at 0.51 mg/L. The death occurred almost in all cases during the exposure period. The calculated LC50 values obtained were:

LC₅₀Males = 1.09  mg/L  

LC₅₀Females = 2.93 mg/L

Test item-related clinical signs recorded during the course of the study consisted in laboured, gasping and/or noisy respiration, respiratory rate increased, sneezing, decreased activity, ataxia, hunched posture, weak and/or wasted condition. Mainly all clinical signs were ceased in the surviving animals from the second week of the observation period.

Normal bodyweight gain was noted for the surviving animals during the observation period in all groups, with the exception of Group 1 (1.04 mg/L) where slight bodyweight loss was recorded in two males during the first three days.

At necropsy, dark/red discoloration of the non-collapsed lungs and white foamy material in the trachea were seen in all found dead animals (n=8) receiving 5.07 and 5.14 mg/L). These findings were associated with enlargement and red discoloration of the liver in five of them and presence of clear/beige liquid at the fur of head or of the perinasal area in four of them. No macroscopic findings were seen in the surviving female.

At 2.52 mg/L and 1.04 mg/L, similar findings were recorded in the lungs, trachea and fur of all found dead animals. No macroscopic findings were seen in the surviving animals.

At 0.51 mg/L, no macroscopic findings were seen in any animals.

 

Under the test conditions, Reaction product of naphthalene, propan-2-ol, 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:

1.09 µg/m³ air

Quality of whole database:

GLP study conducted according to OECD guideline no. 403 (Klimish score = 1)

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 was conducted according to a method equivalent to EU / OECD guidelines and was performed before GLP implementation.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source, Age at study initiation, Weight at study initiation, Housing, Diet, Water, Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature, Humidity, Air changes, Photoperiod: data not available

IN-LIFE DATES: data not available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: no data available
- % coverage: no data available
- Type of wrap if used: a cuff of polyethylene film which encircled the trunk of the animal


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: not applicable


TEST MATERIAL
- Amount(s) applied: 2500, 5000 and 10000 mg/kg
- Concentration (if solution): 2500, 5000 and 10000 mg/kg
- Constant volume or concentration used: not applicable
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied: not applicable
- Concentration: not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable

Duration of exposure:

24 hours

Doses:

2500, 5000 and 10000 mg/kg

No. of animals per sex per dose:

4 animals at 2500 and 5000 mg/kg ; 5 animals at 10000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data available
- Necropsy of survivors performed: yes
- Other examinations performed: local irritation

Statistics:

not applicable

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

ca. 4 200 mg/kg bw

Based on:

test mat.

Mortality:

5 animals died at 10000 mg/kg within the period of exposure. 3/5 animals died at 5000 mg/kg.

Clinical signs:

other: Severe erythema and edema of the skin of the affected area, with capillary hemorrhages and congestion of the larger vessels in the dermis were obserbed at 10000 mg/kg. Skin irritation at the lowest dosage was initially equally severe as that seen at the h

Gross pathology:

The only noteworthy gross pathology, excluding the skin, that was seen at autopsy was somewhat pronounced congestion of the blood vessels of the stomach and small intestine.

Other findings:

No data available

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 the test item sodium isopropylnaphtalene sulfonate was calculated as 4200 mg/kg in rabbits.

Executive summary:

The substance sodium isopropylnaphtalene sulfonate has been tested for acute dermal toxicity in Male Albino rabbits, according to similar O.E.C.D. guideline Nb.402. The test article (75% active) was applied as an aqueous paste to groups of male albino rabbits at doses of 2500, 5000 and 10000 mg/kg bw, respectively under an occlusive dressing applied for 24 hours. At the end of the period of exposure, the cuff and any excess of the dose were removed, and the skin examined for primary irritation for 7 days.

At 10000 mg/kg, 5 animals died within the period of exposure. At 5000 mg/kg, 3/5 animals died. Severe erythema and edema of the skin of the affected area, with capillary hemorrhages and congestion of the larger vessels in the dermis were obserbed at 10000 mg/kg. Skin irritation at the lowest dosage was initially equally severe as that seen at the higher dosages. Over the course of the observation period, edema subsided within 2 to 3 days, but the formerly erythematous areas became blackened and leathery. This appearance persisted until sacrifice at 7 days after the dose.

The only noteworthy gross pathology, excluding the skin, that was seen at autopsy was somewhat pronounced congestion of the blood vessels of the stomach and small intestine.

As the acute dermal LD50 was calculated as 4200 mg/kg under the conditions of the test (i.e 3150 mg/kg in terms of active ingredient), sodium isopropylnaphtalene sulfonate 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:

4 200 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 (1994), the substance reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda has been tested for acute oral toxicity in Sprague Dawley rats, according to O.E.C.D. guideline 401. The test article (76% active), diluted in distilled water, was administered as a single dose of 200, 600 and 1800 mg/kg bw (in terms of test material) to groups of 5 males and 5 females, at a dosing volume of 5 ml/kg. At 200 and 600 mg/kg, no deaths occurred during the observation period. At 1800 mg/kg, one female died after 5 h, 2 males and 3 females died on day 2. Piloerection, decreased motor activity, hypertension and loss of grip were noted in animals treated with 1800 mg/kg at least until the 6th hour of observation. The body weight gain of the surviving males treated with 1800 mg/kg on day 15 was slightly lower (-14%) than other doses, but their weight change was however satisfactory. The surviving female treated with 1800 mg/kg presented a slight weight loss at day 4. The LD50 was determined to be between 600 and 1800 mg/kg bw.

In the supporting study (1957), the substance sodium isopropylnaphtalene sulfonate has been tested for acute oral toxicity in Male Albino rats, similarly to O.E.C.D. guideline 401. The test article (75% active) was administered as a 10% aqueous solution to groups of male albino rats at doses of 630, 1250, 2500 and 5000 mg/kg bw, respectively (in terms of test materal). At 5000 mg/kg, all animals died within one-half hour. At 2500 mg/kg, there was one survivor, the remaining animals died within 1 to 18 hours. Three deaths occurred at 1250 and 630 mg/kg, but only after a period of 6 days following the dose. For the dead animals, severe hemorrhage of the gastrointestinal tract was observed on post-mortem examination. For surviving animals, no significant pathology was found by gross inspection. The LD50 was calculated as 1350 mg/kg.

Acute inhalation toxicity:

One Klimisch score 1 study was available for inhalation route and was used as a key study:

In this study (2013), performed according to the Guideline 403 and in compliance with the GLP, groups of young adult Wistar rats were exposed by inhalation route to aerosol of Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda (powder) for 4 hours at concentrations of 5.07 (sighting study); 0.51, 1.04, 2.52 and 5.14 mg/L.  Animals then were observed for 14days for mortality, clinical signs and bodyweight gain and then euthanized for gross necropsy.

 Premature death was recorded in 3/4 animals dosed at 5.07 mg/L during the sighting exposure and in 2/10, 6/10 and 5/5 rats at dose levels of 1.04, 2.52 and 5.14 mg/L, respectively in the main study. No mortality was reported at 0.51 mg/L. The death occurred almost in all cases during the exposure period.

Test item-related clinical signs recorded during the course of the study consisted in laboured, gasping and/or noisy respiration, respiratory rate increased, sneezing, decreased activity, ataxia, hunched posture, weak and/or wasted condition. Mainly all clinical signs were ceased in the surviving animals from the second week of the observation period. Normal bodyweight gain was noted for the surviving animals during the observation period in all groups, with the exception of Group 1 (1.04 mg/L) where slight bodyweight loss was recorded in two males during the first three days. At necropsy, dark/red discoloration of the non-collapsed lungs and white foamy material in the trachea were seen in all found dead animals (n=8) receiving 5.07 and 5.14 mg/L). These findings were associated with enlargement and red discoloration of the liver in five of them and presence of clear/beige liquid at the fur of head or of the perinasal area in four of them. No macroscopic findings were seen in the surviving female. At 2.52 mg/L and 1.04 mg/L, similar findings were recorded in the lungs, trachea and fur of all found dead animals. No macroscopic findings were seen in the surviving animals. At 0.51 mg/L, no macroscopic findings were seen in any animal.

The LC50 was calculated as 1.09 mg/L in male rats and as 2.93 mg/L in female rats.

Acute dermal toxicity:

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

In this study (1954), the substance sodium isopropylnaphtalene sulfonate has been tested for acute dermal toxicity in Male Albino rabbits, according to a protocol similar to O.E.C.D. guideline 402. The test article (75% active) was applied as an aqueous paste to groups of male albino rabbits at doses of 2500, 5000 and 10000 mg/kg bw (in terms of test material), respectively under an occlusive dressing applied for 24 hours. At 10000 mg/kg, 5 animals died within the period of exposure. At 5000 mg/kg, 3/5 animals died. Severe erythema and edema of the skin of the affected area, with capillary hemorrhages and congestion of the larger vessels in the dermis were obserbed at 10000 mg/kg. Skin irritation at the lowest dosage was initially equally severe as that seen at the higher dosages. Over the course of the observation period, edema subsided within 2 to 3 days, but the formerly erythematous areas became blackened and leathery. This appearance persisted until sacrifice at 7 days after the dose. The only noteworthy gross pathology, excluding the skin, that was seen at autopsy was somewhat pronounced congestion of the blood vessels of the stomach and small intestine. The LD50 was calculated as 4200 mg/kg.

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 OECD test guideline and was more recent than the other study (1957) which was thus assigned as supporting study. Furthermore the LD50 obtained in the key study is slightly lower than the one obtained in the supporting study, representing therefore the worst-case.

Justification for selection of acute toxicity – inhalation endpoint
only one study available (GLP and 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.

Self classification:

Reaction product of naphthalene, propan-2-ol, 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 GHS UN as the oral LD50 (rat) is between 600 and 1800 mg/kg.

Reaction product of naphthalene, propan-2-ol, 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 GHS UN as the LC50 male rat (aerosol, 4h) is 1.09 mg/L.

Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is not classified for acute dermal toxicity according to the Regulation (EC) 1272/2008 (CLP) and GHS UN as the dermal LD50 (rabbit) is higher than 2000 mg/kg bw.