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Administrative data

Description of key information

Acute Oral: LD50 = 5000 mg/kg bw (OECD 401)
Acute inhalation LC50 (4h): 50 mg/m³

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:
7 Jul - 21 Jul 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
(Lack of details on test material)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
lack of details on test material.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD (SD) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent
- Age at study initiation: young adult
- Weight at study initiation: 172 g (males) and 143 g (females)
- Fasting period before study: Healthy animals were fasted overnight prior to dosing.
- Housing: Animals were housed in single sex groups of five in grid bottomed polypropylene cages.
- Diet: Commercially available pelleted rodent diet provided, as libitum.
- Water: Mains drinking water via polypropylene bottles provided, ad libitum.
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 43-76
- Air changes (per hr): air conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined frequently after dosing and daily for fourteen consectutive days. Any signs of toxicity or other effects were noted along with the time of onset and duration. Animals were weighed at weekly intervals.
- Necropsy of survivors performed: yes. At the end of the fourteen day observation period surviving animals were weighed and then sacrificed by carbon dioxide narcosis. The sacrificed animals and those dying during the study were subjected to gross examination including the opening of the thoracic and visceral cavities.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
5000 mg/kg bw: 1/5 females died at Day 2
Clinical signs:
No effects of treatment were observed in surviving animals.
Body weight:
All surviving animals gained bodyweight throughout the study.
Mean change in bodyweight for males: 109 g
Mean change in bodyweight for females: 59 g
Gross pathology:
The female animal found dead on Day 2 had been cannibalised and autolysed. No detailed post-mortem examination was possible.
In surviving animals no abnormalities were noted at necropsy.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008.
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study performed with Sodium N-lauroylsarcosinate (CAS 137-16-6).

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:
14 Apr - 11 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
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: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 10-12 weeks
- Weight at study initiation: 324 g (males) and 209 (females)
- Fasting period before study: during exposure to the test substance
- Housing:
Before exposure:
Group housing of five animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material and paper as cage-enrichment
After exposure: Group housing as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the Day of exposure the paper sheet was removed.
- Diet: pelleted rodent diet except during exposure to the test substance, ad libitum
- Water: tap water except during exposure to the test substance, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.8 – 21.5)
- Humidity (%): 40-70 (actual range: 34 – 60)
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: no vehicle
Details on inhalation exposure:
EXPOSURE CHAMBER:
The design of the exposure chamber is based on the flow past nose-only inhalation chamber. The chamber consisted of three or four animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.

TEST ATMOSPHERE GENERATION:
The test substance was fed to a stream of pressurized air (mean air flow 27.6 l/min at 5 mg/L, 19.1 l/min at 1 mg/L, 38.6 l/min at 0.55 mg/L and 110.6 l/min at 0.055 mg/L) by means of a spiral feeder and a micronizing jet mill, which was subsequently was passed through a cyclone, allowing larger particles to settle, before it entered the exposure chamber. The rotation speed of the feeder was varied to obtain the desired exposure concentration.
From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

TEST ATMOSPHERE CHARACTERISATION:
Nominal concentration:
The nominal concentration was calculated by dividing the amount of test substance used by the volume of pressurized air (average air flow times exposure time) entering the exposure chamber used for exposure of the animals.

Actual concentration:
The actual concentration was determined five times during exposure at 5 or 1 mg/L, nine times at 0.55 mg/L and seven times at 0.055 mg/L. Samples were drawn from the test atmosphere through a tube mounted in one of the free animal ports of one of the middle sections of the exposure chamber. Samples were drawn through a glass fiber filter. The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter.

Subsequently the mean concentrations with the standard deviation were calculated.

Particle size characterisation:
The particle size distribution was representatively characterized twice during exposure. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of one of the middle sections of the exposure chamber. The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters and a fiber glass back-up filter. Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.

Stability monitoring:
The opacity of the test atmosphere at the highest concentrations was expected to exceed the maximum that could be monitored by means of an aerosol monitoring system. An indication of the stability of the test atmosphere was obtained from the concentration measurements, which were equally distributed over time. For the lowest concentration, the opacity of the test atmosphere was monitored by means of a real time aerosol monitoring system. Data obtained with this system were used to illustrate the stability of the aerosol during exposure of the animals.

Temperature and relative humidity:
The temperature and relative humidity were measured with a humidity and temperature indicator and were recorded after the animals were placed in the experimental set-up and at 30 minute intervals after initiation of the exposure. The probe was inserted in a tube mounted in one of the free animal ports of the middle section of the exposure chamber. The temperature of the atmosphere was between 18.1 and 21.3°C and relative humidity was between 23 and 41%. These conditions were considered appropriate for this relatively short 4 hours exposure duration.










Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Initially, five animals of each sex were exposed for 4 hours to a target concentration of the test substance of 5 mg/L. Based on mortality, further animals were dosed at 1 mg/L (both sexes), and at 0.5 and 0.05 mg/L using the most sensitive sex (males) only.
No. of animals per sex per dose:
5 males and 5 females at 5.5 mg/L
5 males and 5 females at 1.1 mg/L
5 males at 0.5 and 0.05 mg/L
Control animals:
no
Details on study design:
- Other examinations performed:
Mortality/Viability: Twice daily. Animals showing pain, distress or discomfort, which was considered not transient in nature or was likely to become more severe, were sacrificed for humane reasons. The time of death was recorded as precisely as possible.

Clinical signs (During exposure): Three times during exposure for mortality, behavioural signs of distress and effects on respiration.

Clinical signs (After exposure): Twice (at 1 and at 3 h after exposure) on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Body weights: Days 1 (pre-administration), 2, 4, 8 and 15 and at death (if found dead or sacrificed after Day 1).

Necropsy: The moribund animals and animals surviving to the end of the observation period were sacrificed by an intraperitoneal injection with Euthasol ® (AST Farma BV, Oudewater, The Netherlands) and subsequently exsanguinated. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded. Particular attention was given to any changes in the respiratory tract.









Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.05 - < 0.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
5 mg/L: 5/5 males and 5/5 females died (at 1-2 h post-dose)
1 mg/L: 5/5 males and 5/5 females died (at 1-2 days post-dose)
0.5 mg/L: 4/5 males died (at 1-2 days post-dose)
0.05 mg/L: 0/5 males died
Clinical signs:
other: During exposure: 1 mg/L: most animals showed laboured respiration. No clinical signs were noted during exposure at 5, 0.5 and 0.05 mg/L. After exposure: 5 mg/L: No clinical signs noted prior to death/sacrifice. 1 mg/L: Lethargy, flat/hunched posture, la
Body weight:
Significant weight loss was observed for the single surviving male at 0.5 mg/L (No. 25) between Days 1 and 4. Body weight gain of males at 0.05 mg/L was within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
5 mg/L : Red foci on the lungs, red contents of the small intestines/ileum, red discolouration of the thymus and or small intestines among most animals.
1 mg/L: Red foci on the lungs or red discolouration of the lungs in all animals.
0.5 mg/L: Red foci on the lungs and/or thymus and/or red discolouration of the lungs among most males.
0.05 mg/L: No abnormalities noted.
Other findings:
The concentration measurements, distributed over time, showed that the substance was sufficiently stable. At 0.05 mg/L data was obtained from the opacity monitor and showed that the aerosol was sufficiently stable. The short drops in opacity were caused by adjustments to the generation equipment and were considered not to have affected the exposure level.

Table 1. Test atmosphere characterisation.

 

Target concentration

(mg/L)

 

Actual concentration

(mg/L; mean ± sd)

 

Nominal concentration

(mg/L; mean)

 

 

Generation efficiency (%)

 

5

 

5.4 ± 0.6

 

15.4

 

35

1

1.2 ± 0.1

4.2

29

0.5

0.6 ± 0.2

2.9

21

0.05

 

0.06 ± 0.01

0.05

83

Table 2. Particle Size.

 

Target concentration

(mg/L)      (measurement no.)

 

 

MMAD

 

Gsd

5                             (1)

5.8

3.2

                               (2)

6.2

2.6

1                             (1)

3.5

4.4

                               (2)

3.8

4.0

0.5                          (1)

2.5

2.5

                               (2)

3.2

3.4

0.05                        (1)

4.1

2.4

                               (2)

4.6

2.9

MMAD: Mass Medium Aerodynamic Diameter

gsd: geometric standard deviation

Table 3. Table for acute inhalation toxicity.

Target concentration
[mg/L air]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

5

5/5/5

---

1-1.5 h after start of exposure

100

1

5/5/5

 

2 h after start of exposure

100

0.5

4/5/5

 

Day 1-2

80

0.05

0/0/5

 

0

Females

5

5/5/5

---

2 h after start of exposure

100

1

5/3/5

 

2-4.5 h after start of exposure

100

LC50 0.05-0.5 mg/L air

*first number = number of dead animals

second number = number of animals with clinical signs

third number = number of animals used

Interpretation of results:
other: Acute tox. Inhalation 2, H330. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS).
Conclusions:
CLP: Acute Tox. 2, H330


Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
50 mg/m³
Quality of whole database:
The available information comprises an adequate and reliable study performed with Sodium N-lauroylsarcosinate (CAS 137-16-6).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Discussion

Acute oral

The acute toxicity via the oral route of Sodium N-lauroylsarcosinate (CAS 137-16-6) has been investigated in rats in accordance with OECD guideline 401 under GLP conditions (Toxicol Laboratories Ltd, 1987a, AOT).

A group of 10 Sprague Dawley rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance by gavage. The observation period following administration was 14 days. During the study period, one female animal died at Day 2. No clinical signs of toxicity were observed in the surviving animals. All surviving animals showed normal body weight gain. The female animal found dead had been cannibalised and autolysed. Thus, no detailed post-mortem examination was possible. In surviving animals no abnormalities were noted at necropsy.

Thus, the oral LD50 for male and female rats is greater than 5000 mg/kg bw.

 

Acute inhalation

Two studies are available to investigate the acute inhalation toxicity potential of Sodium N-lauroylsarcosinate (CAS 137-16-6).

In the first available study (Notox B.V., 2010a, AIT), conducted according to OECD guideline 403 and in compliance with GLP, Wistar rats were treated with the neat test material (96.2% purity) via nose-only inhalation exposure for 4 h. 5 males and 5 females each were exposed to concentrations of 5 and 1 mg/L, and 5 males each were exposed to concentrations of 0.55 and 0.055 mg/L. The powdered test material was fed to a stream of pressurised air to generate the test atmosphere. The animals were observed for mortality, clinical signs and effects on body weights for a period of 14 days following administration. At study termination, the animals were submitted to gross pathological examination. All animals of the 5 and 1 mg/L dose groups died within 1-2 h post-exposure. At 0.5 mg/L 4/5 males died within 1-2 days post-exposure. No mortality was noted in the low dose group (0.05 mg/L) throughout the study period. During exposure, animals of the 1 mg/L dose group showed laboured respiration. No clinical signs were noted during exposure in any animal of the remaining dose groups. After exposure, animals treated with 5 mg/L showed no clinical signs prior to death/sacrifice. At 1 mg/L lethargy, flat/hunched posture, laboured respiration, piloerection and red discolouration of the mouth and nose was noted among most females. No clinical signs were observed among males. At 0.5 mg/L lethargy, flat/hunched posture, laboured respiration, piloerection and red discolouration of the nose, and/or moribund condition was reported for males. No clinical signs were noted in males treated with 0.05 mg/L test material. Significant weight loss was observed for the single surviving male at 0.5 mg/L between Days 1 and 4. Body weight gain of males at 0.05 mg/L was within the range expected for rats of this strain and age used in this type of study. Gross pathology revealed red foci on the lungs, red contents of the small intestines/ileum, red discolouration of the thymus and or small intestines among most animals exposed to 5 mg/L. All animals of the 1 mg/L dose group showed red foci on the lungs or red discolouration of the lungs. Red foci on the lungs and/or thymus and/or red discolouration of the lungs were noted among most males treated with 0.5 mg/L test material. No abnormalities were noted in males exposed to a concentration of 0.05 mg/L. Based on the result of this study, the LC50 for both males and females for the neat, pulverised test substance was 0.05-0.5 mg/L. The neat test material meets therefore the criteria to be classified for acute inhalation toxicity Cat. 2, H330 according to Regulation (EC) No 1272/2008.

The second available study (WIL Research Europe B.V., 2013, AIT) was performed according to the OECD test guideline 403 and in compliance with GLP. Five Wistar rats per sex per dose were exposed to an aerosol of a 34.5% aqueous solution of Sodium N-lauroylsarcosinate (CAS 137-16-6) in a nose-only inhalation apparatus for 4 h. To generate the test atmosphere at concentrations of 0.5, 1 and 5 mg/L, the test material was nebulised and diluted with pressurised air, before entering the exposure chamber. Following treatment, the animals were observed for a period of 14 days following administration. Additionally to the recommended observations and examinations (mortality, clinical signs, body weights, gross pathology), histopathological examination of low and high dose animals was performed with special focus on the respiratory tract in order to consider the influence of the well-known irritant characteristics of the test substance on the results. No mortality occurred after exposure to 0.5 or 1 mg/L. At 5 mg/L, two females and three males were found dead immediately following the exposure, and the remaining animals were sacrificed for humane reasons within 1 hour after exposure. No further mortalities occurred throughout the study period. Clinical signs noted during exposure with 0.5 mg/L were shallow respiration in all animals. After exposure, the only clinical sign noted was the chromodacryorrhoea of the snout in one male on Day 2. At 1 mg/L, shallow respiration was noted in all animals during exposure. After exposure, hunched posture, slow breathing and/or piloerection was noted among all animals between Days 1 and 3. Slow breathing and laboured respiration were seen in all animals during treatment with 5 mg/L. After exposure, lethargy, hunched posture, slow breathing, laboured respiration and/or piloerection were observed in the animals that were sacrificed for humane reasons on the day of exposure. The overall body weight gain in surviving males and females was within the range expected for rats of this strain and age used in this type of study. Macroscopic post mortem examination of the animals revealed the following findings that were considered to be treatment-related: at 5 mg/L lungs with watery cloudy content were noted in 1/5 males and 4/5 females; the microscopic correlate was alveolar fibrinous material. The thymus was found to be dark red or with reddish foci in 5/5 males and 5/5 females; the microscopic correlate was congestion. The mandibular lymph nodes showed reddish discolouration in 3/5 males and 2/5 females; the microscopic correlate was congestion and erythrophagocytosis. In animals exposed to 1 mg/L the thymuses were found with reddish discolouration and dark red foci in 1/5 males and 1/5 females. The lung was reddish discoloured in 1/5 males. At 0.5 mg/L no treatment related findings were noted. Histopathological examination revealed local effects on the respiratory tract. Erosion in the trachea was present in one female treated with 0.5 mg/L at minimal degree and in most males and all females treated with 5 mg/L up to marked degree. Epithelial degeneration of the trachea with loss of cilia was present in all males and females treated with 5 mg/L up to moderate degree. Trachea ulceration was present in one male exposed to 5 mg/L at slight degree. Perivascular oedema of the lung was present in one female treated with 0.5 mg/L at slight degree and in most males and females of the 5 mg/L dose group up to moderate degree. Alveolar ectasia of the lung was present in one female treated with 0.5 mg/L at minimal degree and in all males and some females exposed to 5 mg/L at minimal degrees. All males and females treated with 5 mg/L showed alveolar fibrinous material in the lungs up to moderate degree. Epithelial necrosis of the larynx was noted in all males and females treated with 5 mg/L at marked degree; and granulocytic inflammation of the larynx up to slight degree was reported for all males and females exposed to 5 mg/L. Epithelial necrosis of the nasal pharynx (nasopharynx) up to massive degree was present in all males and females treated with 5 mg/L. The findings in the rats of the 5 mg/L dose group were considered to be markers of acute respiratory tract irritancy caused by the test item. The lack of findings in the males, and the few remaining lung and trachea findings in the females treated at 0.5 mg/L indicate that there was either no direct damage and/or good recovery. There was no indication for systemic toxicity. Based on the outcome of this study, the LC50 for both males and females for the 34.5% aqueous solution of the test substance, is 1-5 mg/L. The 34.5% aqueous solution of the test substance meets therefore the criteria to be classified for acute inhalation toxicity Cat. 4, H332 according to Regulation (EC) No 1272/2008.

The substance is not produced or marketed in neat form. It is only produced and marketed as aqueous formulations at concentrations of approx. 35% and below. Therefore, the second study performed with a 34.5% aqueous formulation of Sodium N-lauroylsarcosinate (CAS 137-16-6), which is the highest technically attainable concentration during the manufacturing process, more closely reflects the potential for acute inhalation toxicity under realistic conditions and at concentrations relevant for human exposure. The data obtained from this study is used to determine specific concentration limits and to derive a classification for the marketed product.

 

Acute dermal

According to Regulation (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The information mentioned in section 8.5.2, acute inhalation toxicity study is provided. Furthermore, testing by the dermal route is not deemed appropriate as the physicochemical properties of the registered substance suggest a low rate of absorption through the skin.

Justification for classification or non-classification

The available data on acute oral toxicity of Sodium N-lauroylsarcosinate (CAS 137-16-6) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.

The available data on the acute inhalation toxicity of Sodium N-lauroylsarcosinate (CAS 137-16-6) meet the criteria for classification for Acute toxicity - inhalation category 4 (H332) according to Regulation (EC) No 1272/2008 at concentrations up to 34.5%. Furthermore, at concentrations > 34.5% the test item meets the criteria for classification for acute inhalation toxicity Cat. 2, H330 according to Regulation (EC) No 1272/2008. Therefore, Sodium N-lauroylsarcosinate (CAS 137-16-6) is classified accordingly.