Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7 odd-numbered alkyl) derivs. and sodium hydroxide and chloroacetic acid

Endpoint summary

Description of key information

Three reliable studies are available on the acute oral toxicity of Amphoacetates C8. One was performed in rats and one in mice with an aqueous solution of disodium caprylo amphodiacetate, and one study was performed 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 with a substance analogue showed that the analoge was not toxic via the dermal route. This result is read across, the rationale to read across the data isattached in Section 13.

An acute inhalation study was waived since exposure via inhalation is not considered a relevant route of exposure and information on the toxicity via two relevant routes is available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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

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 or test system 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:

other: No clinical signs

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.

Reference 2

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 or test system 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:

other: 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.

Reference 3

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 or test system 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:

other: 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:

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

Reason / purpose for cross-reference:

read-across source

Sex:

female

Preliminary study:

Not applicable

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:

other: 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

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)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available study was considered reliable (Klimisch 1 study).

Additional information

Three reliable studies 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.

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 bw and the dermal LD50 was considered to exceed 2000 mg/kg bw. Therefore no classification according to CLP or UN-GHS criteria is warranted.