Registration Dossier

Administrative data

Description of key information

Three reliable studies are available on the acute oral toxicity of C8 Amphoacetates. One performed in rats and one in mice with an aqueous solution of disodium caprylo amphodiacetate, and one in mice with an anhydrous form of the same product. The resulting oral LD50's show that the oral LD50 can reasonably be considered to be higher than 5000 mg/kg bw.

An acute dermal toxicity study conducted with a member of the chemical category 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

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Study in accordance with US FHSA/CPSC design, 16 CFR 1500 for Acute Oral Toxicity testing
Qualifier:
according to
Guideline:
other: FHSA/CPSC Design, 16 CFR 1500 for Acute Oral Toxicity testing
Principles of method if other than guideline:
Oral (gavage) administration of 5000 mg/kg of test item to rats, followed by 14-day observation
GLP compliance:
yes
Test type:
other: estimated LD50
Limit test:
yes
Specific details on test material used for the study:
Trade name: Mackam 2CY-75
Purity: 15% solids (active and impurities)
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: L-48049
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Indianapolis, Indiana
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: 200-245 grams
- Fasting period before study: overnight prior to dosing
- Housing: individually in stainless steel cages

ENVIRONMENTAL CONDITIONS
- Temperature, humidity and light controlled room (no details provided)

IN-LIFE DATES: No details provided
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5 mL/kg (globally equivalent to 5000 mg/kg of commercial product, i.e. 750 mg/kg of solid content)
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: frequently on the day of dosing
- Weighing: prior to dosing and at the end of the 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 750 mg/kg bw
Based on:
other: solid content
Mortality:
No mortality
Clinical signs:
No clinical signs
Body weight:
No significant body weight changes
Gross pathology:
No significant findings
Interpretation of results:
study cannot be used for classification
Conclusions:
The oral LD50 in rats was higher than 5 mL/kg, globally equivalent to 750 mg/kg expressed as solid content.
Executive summary:

Disodium caprylo amphodiacetate, as Mackam 2CY-75, 15% solids, was tested for acute oral toxicity in Sprague-Dawley rats.  The test article was administered as such by gavage as a single oral dose at 5 mL/kg dose volume to 5 rats per gender fasted overnight. Examinations for mortality and clinical signs were performed daily for 14 days. A complete gross necropsy was performed at sacrifice.

No mortality or clinical changes were observed over the observation period.

Under the conditions of the experiment, the oral LD50 was higher than 5 mL/kg, globally equivalent to 750 mg/kg expressed as solid content assuming a specific gravity of 1.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Only one-page summary report available
Qualifier:
no guideline followed
Principles of method if other than guideline:
Following a single oral administration of the test material the mice were observed for 5 days.
GLP compliance:
no
Test type:
other: estimated LD50
Limit test:
no
Specific details on test material used for the study:
Trade name: Miranol J2M Conc
Purity: not specified
Typical solid content (active + impurities) for the commercial product: 49%
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: 2902D77
Species:
mouse
Strain:
other: Carworth
Sex:
not specified
Details on test animals and environmental conditions:
Normal, healthy CFW mice, weighing 18 to 21 grams, maintained in wire cages (5 per cage), with ad limitum acess to feed and water.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
10 and 15 mL/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: no
- Other examinations performed: not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 15 mL/kg bw
Based on:
test mat.
Mortality:
One mouse given 15 mL/kg died (no details provided)
Clinical signs:
No details
Interpretation of results:
study cannot be used for classification
Conclusions:
The oral LD50 in mice was higher than 15 mL/kg, globally equivalent to 7350 mg/kg expressed as solid content.
Executive summary:

Disodium caprylo amphodiacetate, as Miranol J2M Conc, was tested for acute oral toxicity in Carworth mice.  The test article was administered as such by gavage as a single oral dose at 10 or 15 mL/kg dose volume to 10 mice per dose level. The animals were observed for 5 days.

One mouse given 15 mL/kg died in the course of the observation period.

Under the conditions of the experiment, the oral LD50 was higher than 15 mL/kg, globally equivalent to 7350 mg/kg expressed as solid content assuming a specific gravity of 1 and a 51% water content in the aqueous solution tested.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Only one-page summary report available
Qualifier:
no guideline followed
Principles of method if other than guideline:
Following a single oral administration of the test material the mice were observed for 5 days.
GLP compliance:
no
Test type:
other: estimated LD50
Limit test:
no
Specific details on test material used for the study:
Trade name: Miranol J2M Anhydrous Acid
Purity: not specified (assumed to be ca. 100% solid content)
Chemical active ingredient: Disodium caprylo amphoacetate
CAS No.: 68608-64-0
Batch No.: 5958D80
Physical form: orange colored viscous gel
Species:
mouse
Strain:
Swiss Webster
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sunrise Lab Animals
- Age at study initiation:
- Weight at study initiation: 20-35 g
- Fasting period before study: 18 hours
- Housing: individually in stainless steel wire bottomed cages
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-72
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours of fluorescent light daily

IN-LIFE DATES: Not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
7500, 8500 and 9500 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: no
- Other examinations performed: not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 8 200 mg/kg bw
Based on:
test mat.
Mortality:
Group mortality rates were:
- 10% at 7500 mg/kg (1/5 M + 0/5 F)
- 90% at 8500 mg/kg (5/5 M + 4/5 F)
- 80% at 9500 mg/kg (4/5 M + 4/5 F)
Clinical signs:
Nothing remarkable
Gross pathology:
Not applicable
Interpretation of results:
study cannot be used for classification
Conclusions:
The oral LD50 in mice was 8200 mg/kg expressed as anhydrous product.
Executive summary:

Disodium caprylo amphodiacetate, as Miranol J2M Anhydrous Acid, was tested for acute oral toxicity in Swiss-Webster mice.  The test article was administered as such by gavage as a single oral dose at 7500, 8500 or 9500 mg/kg dose volume to 5 mice per gender and dose level. The animals were observed for 5 days.

The mortality rate was 10%, 90% or 80% at 7500, 8500 or 9500 mg/kg, respectively.

Under the conditions of the experiment, the oral LD50 was 8200 mg/kg expressed as anhydrous product.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
3 studies in accordance with national standards at the time of the experiments.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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:
In Section 13 of the IUCLID dossier, a report is attached in which the category approach is reported according to ECHA Guidance for the implementation of REACH, Guidance on information requirements and chemical safety assessment, Chapter R.6 (reporting format for a chemical category).
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:
The dermal acute LD50 (rat) of Alkylamidoamine glycinate maj. C12-14 (amphoacetate; C8-C18 alkyl derivatives) was found to exceed 2612 mg/kg bw (expressed as solid content). This result is read across to C8 Amphoacetates.
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 C8 Amphoacetates.

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 toxicit, oral:

3 studies of appropriate reliability are available: one performed in rats and one in mice with an aqueous solution of disodium caprylo amphodiacetate, and one in mice with an anhydrous form of the same product. The resulting oral LD50's are as follows:

Rats, aqueous solution: > 750 mg/kg solid content;

Mice, aqueous solution: > 7350 mg/kg solid content;

Mice, anhydrous acid: 8200 mg/kg.

Overall, based on these experimental results and the 2017 CESIO recommendations for CAS 68608-64-0, the oral LD50 can reasonably be considered to be higher than 5000 mg/kg bw.

Acute toxicity: dermal

An acute dermal toxicity study (limit test) was conducted with a related member of the chemical category (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 read-across from this member of the chemical category alkylamphoacetates to the registered substance for the acute dermal toxicity of the substance is considered scientifically justified based on the overall information available (see report for the category approach in IUCLID chapter 13).

Justification for classification or non-classification

Based on these experimental results and the 2017 CESIO recommendations for CAS 68608-64-0, the oral LD50 is considered to be higher than 5000 mg/kg. Therefore no classification according to CLP or UN-GHS criteria is warranted.

In accordance with the CLP Regulation the substance is not classified for dermal toxicity as the LD50 oral in rats determined to be more than 2612 mg/kg bw.