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Toxicological information

Acute Toxicity: inhalation

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Administrative data

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
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2013

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda
EC Number:
939-368-0
Cas Number:
1322-93-6
Molecular formula:
Not applicable (a generic molecular formula can not be provided for this specific UVCB substance)
IUPAC Name:
Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Supragil WP
- Stability under test conditions: no data
- Storage condition of test material: Room temperature, protected from humidity

Test animals

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

Administration / exposure

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

Results and discussion

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.
Effect levelsopen allclose all
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

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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.