Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11th December 2017 to 28th December 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Dilithium tetraborate
EC Number:
234-514-3
EC Name:
Dilithium tetraborate
Cas Number:
12007-60-2
Molecular formula:
B4Li2O7
IUPAC Name:
dilithium(1+) bicyclo[3.3.1]tetraboroxane-3,7-bis(olate)
Test material form:
solid: bulk

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 20 to 21°C with an actual daily mean relative humidity of 43 to 50%. A 12 hour light/12 hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1%
Details on dermal exposure:
A single dose of test item was administered to the appropriate animals by dermal application on Day 1. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test item 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. The application period was 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg (bw)
No. of animals per sex per dose:
5 males and 5 females (females were nulliparous and non-pregnant).
Control animals:
no
Details on study design:
Dilithium tetraborate was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Red discoloration of the nose was noted for one male and one female on Days 1 and/or 2 and chromodacryorrhoea of the snout was noted for two males and on female on Day 2.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

TABLE 1 MORTALITY DATA


 
TEST DAY
HOURS AFTER TREATMENT
 

 
1
0
 

 
1
2
 

 
1
4
 

 
2

 

 
3

 

 
4

 

 
5

 

 
6

 

 
7

 

 
8

 

 
9

 

 
10

 

 
11

 

 
12

 

 
13

 

 
14

 

 
15

 

'

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MALES 2000 MG/KG

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

FEMALES 2000 MG/KG

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

TABLE 2 CLINICAL SIGNS


 
TEST DAY
HOURS AFTER TREATMENT
 

 

MAX
GRADE
 

 
1
0

 

 
1
2

 

 
1
4

 

 
2

 

 
3

 

 
4

 

 
5

 

 
6

 

 
7

 

 
8

 

 
9

 

 
10

 

 
11

 

 
12

 

 
13

 

 
14

 

 
15

 

'


MALES 2000 MG/KG

ANIMAL 1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Secretion / excretion

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Chromodacryorrhoea (Snout)

(3)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Red discolouration (Nose)

(1)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Secretion / excretion

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Chromodacryorrhoea (Snout)

(3)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

No clinical signs noted

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

No clinical signs noted

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.


FEMALES 2000 MG/KG

ANIMAL 6

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 General erythema (Treated skin)

(4)

-

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

.

 Scales (Treated skin)

(3)

-

-

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

.

ANIMAL 7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 General erythema (Treated skin)

(4)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 8

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 General erythema (Treated skin)

(4)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 Red discolouration (Nose)

(1)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 9

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 General erythema (Treated skin)

(4)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

ANIMAL 10

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

Skin / fur

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 General erythema (Treated skin)

(4)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

Secretion / excretion

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

.

 Chromodacryorrhoea (Snout)

(3)

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

-

.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

- = Sign not observed

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TABLE 3: MACROSCOPIC FINDINGS

 
ANIMAL
 

 
FINDING
 

 
DAY OF DEATH
 

MALES 2000 MG/KG

1

No findings noted

Scheduled necropsy

Day 15 after treatment

2

No findings noted

Scheduled necropsy

Day 15 after treatment

3

No findings noted

Scheduled necropsy

Day 15 after treatment

4

No findings noted

Scheduled necropsy

Day 15 after treatment

5

No findings noted

Scheduled necropsy

Day 15 after treatment

FEMALES 2000 MG/KG

6

No findings noted

Scheduled necropsy

Day 15 after treatment

7

No findings noted

Scheduled necropsy

Day 15 after treatment

8

No findings noted

Scheduled necropsy

Day 15 after treatment

9

No findings noted

Scheduled necropsy

Day 15 after treatment

10

No findings noted

Scheduled necropsy

Day 15 after treatment

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Dilithium tetraborate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results, dilithium tetraborate does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
Executive summary:

Dilithium tetraborate was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No deaths or abnormalities were found at macroscopic post mortem examination of the animals. Based on these results, dilithium tetraborate does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).