Lithium nickel potassium oxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2017 to March 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Japan MAFF 8147, 2000

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lithium nickel potassium oxide

Cas Number:

210352-95-7

Molecular formula:

Li.K.Ni.O.H2O

IUPAC Name:

Lithium nickel potassium oxide

Test material form:

solid: particulate/powder

Details on test material:

Lithium nickel potassium oxide (KDLNO)
CAS Number:
210352-95-7
Appearance/Physical state:
Black powder
Storage: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Test species / strain / quality: Rat / Wistar / Crl:WI (Han) SPF Reasons for selection of the test species: Rats were selected since this rodent species is recommended in the respective test guidelines.

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test species / strain / quality:
Rat / Wistar / Crl:WI (Han) SPF
Reasons for selection of the test species:
Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
Age on day 0:
Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
Sex:
Males and females
The female animals were nulliparous and non-pregnant
Supplier:
Charles River Wiga GmbH, Germany
Arrival in the testing facility:
Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification:
Individual identification by cage cards and tail marking.
Body weight on day 0:
Animals of comparable weight (± 20% of the mean weight, actual weights )

HOUSING AND DIET
Room temperature / relative humidity:
The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Air changes per hour
Approx. 10
Day / night rhythm:
12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage:
Makrolon cage, type III
Number of animals per cage:
Single housing
Feeding:
VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
Drinking water:
Tap water ad libitum
Bedding:
H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
Enrichment:
Wooden gnawing blocks (Type NGM E-022); ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

Conduct of the study
Clipping of the fur:
About 24 hours before application
Route of application:
Single application to the clipped skin (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing* for 24 hours. Afterwards removal of the semi-occlusive dressing, rinsing of the application site with warm water**.
Application area:
About 40 cm² (corresponds to at least 10% of the body surface)
Time of day of application:
In the morning
Observation period:
14 days
Body weight determination:
Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
Clinical observations:
Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
Scoring of skin findings:
Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
Mortality:
A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
Pathology:
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.

* The test item was covered with an 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).
** The removal of the semi-occlusive dressing and the rinsing of the application site with warm water were documented together in a protocol by confirming the time of the removal of the dressing.

Assessment of skin reactions
The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity." Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959): 46-59. Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas:

Erythema and eschar formation
Grading
0
No erythema
1
Very slight erythema (barely perceptible)
2
Well- defined erythema
3
Moderate to severe erythema
4
Severe erythema (beet redness) to eschar formation preventing grading of erythema
Edema formation
Grading
0
No edema
1
Very slight edema (barely perceptible)
2
Slight edema (edges of area well- defined by definite raising)
3
Moderate edema (raised approx. 1 mm)
4
Severe edema (raised more than 1 mm and extending beyond area of exposure)
Descriptions of any dermal findings not covered by this scale were recorded.

Duration of exposure:

Single application to the clipped skin (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing for 24 hours.

Doses:

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 2000 mg/kg bw of KDLNO (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

No. of animals per sex per dose:

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 2000 mg/kg bw of KDLNO (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

Details on study design:

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 2000 mg/kg bw of KDLNO (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

Conduct of the study
Clipping of the fur:
About 24 hours before application
Route of application:
Single application to the clipped skin (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing* for 24 hours. Afterwards removal of the semi-occlusive dressing, rinsing of the application site with warm water**.
Application area:
About 40 cm² (corresponds to at least 10% of the body surface)
Time of day of application:
In the morning
Observation period:
14 days
Body weight determination:
Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
Clinical observations:
Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
Scoring of skin findings:
Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
Mortality:
A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
Pathology:
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.

* The test item was covered with an 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).
** The removal of the semi-occlusive dressing and the rinsing of the application site with warm water were documented together in a protocol by confirming the time of the removal of the dressing.

Assessment of skin reactions
The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity." Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959): 46-59. Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas:

Erythema and eschar formation
Grading
0
No erythema
1
Very slight erythema (barely perceptible)
2
Well- defined erythema
3
Moderate to severe erythema
4
Severe erythema (beet redness) to eschar formation preventing grading of erythema
Edema formation
Grading
0
No edema
1
Very slight edema (barely perceptible)
2
Slight edema (edges of area well- defined by definite raising)
3
Moderate edema (raised approx. 1 mm)
4
Severe edema (raised more than 1 mm and extending beyond area of exposure)
Descriptions of any dermal findings not covered by this scale were recorded.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Systemic effects No systemic clinical signs were observed during clinical examination. Local effects Due to the black discoloration of the application site, no erythema could be determined in the animals from study day 1 until study day 6. Thereafte,r no

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

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 2000 mg/kg bw of KDLNO (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

 No mortality occurred.
 No signs of systemic toxicity were observed in the animals.
 Due to the black discoloration of the application site, no erythema could be determined from study day 1 until study day 6. Thereafter, no local findings were seen in all animals.
 The body weight in all male animals and in two out of five female animals increased within the normal range throughout the study period.
The body weight of two female animals slightly decreased or stagnated during the first week, but increased within the normal range during the second week, while another female showed stagnation of body weight throughout the study period. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.
 No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females).

Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw