Potassium N,N-dimethylglycinate

Endpoint summary

Description of key information

LD50 (oral) > 2250 mg/kg bw (BASF AG, 1979)
LD50 (dermal) > 2000 mg/kg bw (BASF SE, 2015)

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:

1978-09-12 to 1978-09-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study report

Principles of method if other than guideline:

according to BASF-internal standard

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Weight at study initiation: males: 220 - 260 g; females: 180 - 190 g
- Fasting period before study: 15 to 20 hours before application
- Diet: standardized animal laboratory diet

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 21.5 and 50 % (G/V)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2150 and 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: One female in the 5000 mg/kg group was found dead after one day.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 250 mg/kg bw

Based on:

act. ingr.

Mortality:

Male animals: no deaths after 14 days
Female animals: 2150 mg/kg: no deaths after 14 days; 5000 mg/kg: 1/5 after 14 days

Clinical signs:

other: 5000 mg/kg: staggering, dyspnea, apathy, poor general state

Gross pathology:

Sacrificed animals: nothing abnormal detected

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 250 mg/kg bw

Quality of whole database:

scientifically acceptable study report

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:

experimental study

Adequacy of study:

key study

Study period:

2015-02-23 to 2015-2015-03-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant study report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

(1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: males: 220.8 ± 6.9 g; females: 204.2 ± 7.3 g
- Housing: Single housing in Makrolon cage, type III
- Diet: ad libitum (VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

deionized

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal and dorsolateral parts of the trunk
- coverage: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: Rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.88 mL/kg bw
- Concentration (if solution): 80 g/100 mL

Duration of exposure:

24 hours

Doses:

2300 mg/kg bw corresponding to an actual dose of 2000 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed throughout the study period.

Clinical signs:

other: No systemic clinical signs were observed in both male and female animals. The following local effects were observed in male and female animals: Males: Well-defined erythema (grade 2) was noted in all male animals from study day 1 until study day 3, which

Gross pathology:

No macroscopic pathologic abnormalities were noted in all animals (5 males and 5 females) examined on the last day of observation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study report.

Additional information

Acute Oral Toxicity

In a study according to BASF internal standard procedures, the acute oral toxicity of the test substance following a single oral administration in Wistar rats was investigated (BASF AG, 1979). Two groups of 10 fasted animals (5 animals per sex and dose) were exposed to 2150 and 5000 mg/kg bw of unchanged test substance (45% solution) and observed for 14 days. One animal of the 5000 mg/kg bw dose group was found dead. All other animals survived until the end of the observation period. At the dose level of 2150 mg/kg bw no clinical signs were observed during the course of the study. The animals of the 5000 mg/kg bw group developed staggering, dyspnoe, apathy and were in a bad general state. The mean body weight increased within the normal range throughout the study period. No macroscopic findings were observed at necropsy. The acute oral LD50 of the test substance after single oral administration to rats is > 5000 mg/kg bw (LD50 of active ingredient = 2250 mg/kg bw).

Acute Dermal Toxicity

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2300 mg/kg bw (actual dose of 2000 mg/kg bw taking the content of active ingredient at study start into account) of Potassium N,N-dimethylglycinate (as suspension in deionized water). The test substance was applied to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

No mortality occurred. No signs of systemic toxicity were observed. The following test item-related local effects were recorded during the whole course of the study (14 days):

- Very slight to well-defined erythema (grade 1 to 2)

- Very slight edema (grade 1)

- Scaling

- Incrustations

- Plaque-like incrustations beyond the application area in one female animal

- Erythema beyond the application area in one female animal

The mean body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals increased within the normal range throughout the study period with two exceptions. Two female animals showed stagnation of body weight during the first week, but the body weight increased within the normal range during the second week. As stagnation of body weight is generally known to occur as a consequence of the dermal application procedure in female animals, the body weight stagnation observed is considered to be unspecific.

No macroscopic pathologic abnormalities were noted in all animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be above 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
scientifically acceptable study report

Justification for selection of acute toxicity – dermal endpoint
GLP and guideline compliant study report.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221.