Registration Dossier

Administrative data

Description of key information

Several acute oral toxicity studies are available.

In the key study, conducted equivalent to OECD 401, the LD50 in rats was determined to be 3422 mg/kg (based on solid content).

An acute dermal toxicity study conducted with a substance analogue in accordance with OECD 402 and according to GLP principles was considered appropriate to determine the acute dermal toxicity of the substance. The acute dermal toxicity was determined to be above 2612 mg/kg in a limit test.

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:
November 9, 1976 - December 21, 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
lack of study design details in the report, observation period of only 7 days, no body weight measurements, no data about the clinical examinations and necropsy
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: no data
- Weight at study initiation: 200-300 g
- Fasting period before study: 18 hours
- Housing: Raised wire mesh cages
- Diet (e.g. ad libitum): Lab Blox ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): air conditioned quarters
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
The test material was diluted 1+1 (w/w) with water just prior to dosing.
Doses:
5.0, 5.5, 6.25 and 6.5 mL/kg bw (aqueous solution)
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: daily observations (no weighing)
- Necropsy of survivors performed: yes
Statistics:
The method of Litchfield & Wilcoxon (1949) was used for calculating the oral LD50.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5.85 mL/kg bw
Based on:
test mat.
Remarks:
(aqueous solution)
95% CL:
5.4 - 6.3
Remarks on result:
other: Aqueous solution with a solid content of approximately 50%
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 844.5 mg/kg bw
Based on:
test mat.
Remarks:
(aqueous solution)
Remarks on result:
other: Aqueous solution with a solid content of approximately 50%
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 422 mg/kg bw
Based on:
other: expressed as solid content
Remarks on result:
other: Results expressed for the substance
Mortality:
One, three, seven and seven animals died in the group of rats receiving 5.0, 5.5, 6.25 and 6.5 mL/kg bw (aqueous solution), respectively
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data

RESULTS: 

Group

Dose

(mL/kg b.w.)

(aqueous solution)

Mortality

Group mortality

(%)

1

5.0

1/10

10

2

5.5

3/10

30

3

6.25

7/10

70

4

6.5

7/10

70

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study conducted equivalent to OECD 401, the LD50 was determined to be 5.85 mL/kg (aqueous solution), converted to be 6844 mg/kg (as the density is 1.17 g/mL). This would correspond to a LD50 of 3422 mg/kg for the substance.
Executive summary:

The test material was tested as an aqueous solution (ca. 50% solids) for acute oral toxicity in the rat. The test article was administered as a 1:1 dilution in water in a single oral dose at 5.0, 5.5, 6.25, and 6.5 mL/kg dose volumes to groups of 10 fasted rats. Examinations for mortality and clinical signs were performed daily for 7 days. One and 3 animals died in the groups administered 5.0 and 5.5 mL/kg, respectively. Seven animals died in the groups receiving 6.25 and 6.5 mL/kg of the test substance. Based on these results, the acute oral LD50 was calculated to be 5.85 mL/kg (aqueous solution), with 95% confidence limits of 5.4 - 6.3 mL/kg.

With a density documented to be approximately 1.17, the LD50 is estimated to be 6844 mg/kg for the aqueous solution. This corresponds to a LD50 of 3422 mg/kg for the substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 422 mg/kg bw
Quality of whole database:
Five studies are available, all studies have Klimisch score 2.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 236 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 612 mg/kg bw
Based on:
other: expressed as solid content
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
other: expressed as surfactant content
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 dermal ( rat) Alkylamidoamine glycinate maj. C12-14 (amphoacetate; C8-C18 alkyl derivatives): > 2612 mg/kg bw (expressed as solid content). This result is read across to the registered substance.
Executive summary:

An acute dermal toxicity study (limit test) was conducted with Alkylamidoamine glycinate maj. C12-14 (amphoacetate, C8-C18 alkyl derivatives) in accordance with OECD 402 and according to GLP principles. A total of 10 rats (5 males and 5 females) were occlusive exposed to 4.47 mL/kg of an aqueous solution of the substance for 24 hours. The dose level was based on the surfactant content of the substance. One female was found dead on day 2. The majority of surviving animals showed chromodacryorrhoea, laboured respiration, rales, gasping, salivation, piloerection and hypothermia between days 1 and 2. No abnormalities were found at macroscopic post mortem examination of the surviving animals. Beginning autolysis was observed for the female that was found dead on day 2.

Based on the results of this study the substance does not need to be classified for acute dermal toxicity in accordance with the CLP Regulation as the acute dermal toxicity of the substance was determined to be above 2612 mg/kg. This result is read across to the registered substance.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2009 - March 8, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Species: Rat, Wistar strain, Crl:WI (Han) (outbred, SPF-Quality)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Number of animals: 5 males and 5 females (females were nulliparous and non-pregnant)
- Age and body weight: Young adult animals (approx. 11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0ºC (actual range: 18.4 – 21.7ºC), a relative humidity of 40-70% (actual range: 31 - 88%) and 12 hours artificial fluorescent light and 12 hours darkness per day
- Accommodation: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type)
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water

IN-LIFE DATES: From: 15 December 2009 To: 29 December 2009
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure and % coverage: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours (using tap water)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (4.47 mL/kg) body weight,
expressed as surfactant content and 2612 mg/kg, expressed as solid content
Dose volume calculated as: Dose level corrected for content (g/kg) / specific gravity (g/mL).
- Concentration (if solution): N/A; the aqueous solution is tested as such

VEHICLE
Not applicable, the aqueous solution is tested as such
Duration of exposure:
24 hours
Doses:
2000 mg/kg (expressed as surfactant content);
2612 mg/kg (expressed as solid content);
5236 mg/kg (expressed as test material, the aqueous solution)
No. of animals per sex per dose:
Single dosage, on Day 1: 5 males and 5 females (females were nulliparous and non-pregnant)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible.
Body weights: Days 1 (pre-administration), 8 and 15 and at death.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
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).
Necropsy: The animals surviving to the end of the observation period were sacrificed by an oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
Not applicable
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 236 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 612 mg/kg bw
Based on:
other: expressed as solid content
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
other: expressed as surfactant content
Mortality:
One female was found dead on day 2. No further mortality occurred.
Clinical signs:
The majority of surviving animals showed one or more of the following clinical signs between days 1 and 2: Chromodacryorrhoea, laboured respiration, rales, gasping, salivation, piloerection, hypothermia.
Scales (grade 1) were seen in the treated skin-area of 8 out of the 9 surviving animals during the observation period. One animal showed also scales (grade 1) on the left flank.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was within the range expected for rats used in this type of study.
Slight body weight loss or reduced body weight gain was observed for all surviving animals over the first week post-treatment, but animals regained weight over the second week post-treatment.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the surviving animals.
Beginning autolysis was observed for the female that was found dead on day 2.
Other findings:
Not applicable
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 dermal ( rat): > 2612 mg/kg bw (expressed as solid content)
Executive summary:

An acute dermal toxicity study (limit test) was conducted with Alkylamidoamine glycinate maj. C12-14 (amphoacetate) (C8-C18 alkyl derivatives) in accordance with OECD 402 and according to GLP principles. A total of 10 rats (5 males and 5 females) were occlusive exposed to 4.47 mL/kg of an aqueous solution of the substance for 24 hours. The dose level was based on the surfactant content of the substance. One female was found dead on day 2. The majority of surviving animals showed chromodacryorrhoea, laboured respiration, rales, gasping, salivation, piloerection and hypothermia between days 1 and 2. No abnormalities were found at macroscopic post mortem examination of the surviving animals. Beginning autolysis was observed for the female that was found dead on day 2.

Based on the results of this study the substance does not need to be classified for acute dermal toxicity in accordance with the CLP Regulation as the acute dermal toxicity of the substance was determined to be above 2612 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 612 mg/kg bw
Quality of whole database:
One study is available (Klimisch score 1), conducted with a substance analogue.

Additional information

Acute toxicity: oral

In the following table, an overview is provided of the available data.

Method

Reliability

Result

(expressed as aqueous solution)

Result

(expressed for the substance)

(1) Standard (equivalent to OECD 401; in rats)

2

5.85 mL/kg

 

 

 3422 mg/kg 

(2) Standard (equivalent to OECD 401; in mice)

2

12.7 mL/kg

 6116 mg/kg

(3) Standard (equivalent to OECD 401; in rats)

2

>15 mL/kg

 >7500 mg/kg

(4) According to OECD 423 and GLP

(in rats)

2

>2000 mg/kg

 >1000 mg/kg

(5) Standard (equivalent to OECD 401 and GLP; in rats)

2

>2000 mg/kg

 >722 mg/kg

The first study is considered to be the key study as it is the study with the lowest defined value. The test sample used in this study has a solid content of 50%. Using the density of the tested aqueous solution (1.17 g/mL) and solid content, this result in an oral LD50 of 3422 mg/kg for the substance. This value is considered as key value for the chemical safety assessment.

The substance is only produced and marketed in aqueous solutions. All available studies showed a low acute oral toxicity and supported the absence of classification for the commercial aqueous solutions.

Acute toxicity: dermal

An acute dermal toxicity study (limit test) was conducted with a substance analogue (C8-C18 alkyl derivatives) in accordance with OECD 402 and according to GLP principles. A total of 10 rats (5 males and 5 females) were occlusive exposed to 4.47 mL/kg of an aqueous solution of the substance for 24 hours. The dose level was based on the surfactant content of the substance. One female was found dead onday 2.The majority of surviving animals showed chromodacryorrhoea, laboured respiration, rales, gasping, salivation, piloerection and hypothermia between days 1 and 2. No abnormalities were found at macroscopic post mortem examination of the surviving animals. Beginning autolysis was observed for the female that was found dead on day 2. Based on the results of this study the acute dermal toxicity of the substance was determined to be above 2612 mg/kg.

The rationale to read across the data is attached in Section 13.

Justification for classification or non-classification

In accordance with the CLP Regulation the substance is not classified for acute toxicity as the LD50 oral in rats was determined to be 3422 mg/kg and the LD50 dermal in rats was determined to be above 2612 mg/kg bw.