Registration Dossier

Diss Factsheets

Administrative data

Description of key information

oral acute toxicity:
LD50 value is 2900 mg/kg bw (rat) based on the test material (approx. 95% act. ingr.)
dermal acute toxicity:
The LD50 value was determined to be greater than 2000 mg/kg bw in male and female rats based on test material (> 90% act. ingr.).

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:
1980-04-10 and 1980-05-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: similar to OECD guideline 401, non-GLP conform study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif: RAIf
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 to 8 weeks old
- Fasting period before study: overnight
- Housing: housed in groups of 5 in Macrolon cages (type 3), individually marked with picric acid.
- Diet: ad libitum; NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2
- Humidity (%): 55 + 10
- Photoperiod: 10 hours light cycle day

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg, 20 mL/kg

Doses:
1000, 2000, 3000, 5000 mg/kg bw
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: Physical condition and rate of deaths were monitored throughout the whole observation period
- Frequency of weighing: immediately prior to dosing (control weights) and at 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: mortality
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 900 mg/kg bw
Based on:
test mat.
95% CL:
2 257 - 3 997
Mortality:
see any other information on results
Clinical signs:
Sedation, dyspnoea, ruffled fur, diarrhoea and a curved body position was observed at concentrations of 1000, 2000 and 3000 mg/kg.
At the highest concentration of 5000 mg/kg ventral and lateral body positions were additionally observed.
Body weight:
Females: Body weight determined on day 1, 7 and 14 remained unchanged.
Males: Slight body weight gain was observed on day 1, 7 and 14 in a concentration range of 1000 - 5000 mg/kg.
Gross pathology:
No substance related gross organ changes were seen.

Rate of Deaths

Dose mg/kg

Sex

Total number animals in group

Total Number animals dead

Death rate percentage

Time of death after dosing

Hours after dosing

Days after dosing

1

2

3

5

24

2

3

4

5

6

7

14

1000

male

5

0

0

 

 

 

 

 

 

 

 

 

 

 

 

2000

5

2

40

 

 

 

 

2

 

 

 

 

 

 

 

3000

5

2

40

 

 

 

 

2

 

 

 

 

 

 

 

5000

5

4

80

 

 

 

3

 

 

 

 

 

1

 

 

1000

female

5

0

0

 

 

 

 

 

 

 

 

 

 

 

 

2000

5

0

0

 

 

 

 

 

2

 

 

 

 

 

 

3000

5

3

60

 

 

 

 

1

 

 

 

 

 

 

 

5000

5

5

100

 

 

1

4

 

 

 

 

 

 

 

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 900 mg/kg bw
Quality of whole database:
similar to OECD guideline

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:
2015-01-15 and 2015-07-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-conform study according to guideline.
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
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: 220.8 g (male), 199.2 (female)
- Housing: Single housing
- Diet: VRF1(P); SDS Special Diets Services
- Water: tap water ad libitum
- 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:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap: 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 h

TEST MATERIAL
- Amount applied: 3.33 mL/kg bw
- Concentration: 60 g/100 mL

Duration of exposure:
24 h
Doses:
2000 mg/kg bw
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 and weighing: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
- Necropsy of survivors performed: yes
-Other: A check for any dead or moribund animals was made at least once each workday.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
No systemic clinical signs were observed during clinical examination. No local skin effects were observed in the animals. Only on study day 1, blue test item residues were noted on the application area.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period with three exceptions in the female group. These females showed a stagnation of body weight within the first week, but body weights were within the normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP/guideline conform study.

Additional information

Acute oral toxicity:

Key study

An acute oral toxicity study was performed by using healthy random bred rats of the Tif:RAIf strain. The test material (approx. 95% act. ingr.) was administered by gavage to 5 animals per sex in doses of 1000, 2000, 3000 and 5000 mg/kg bw. The animals fasted overnight and were treated by single incubation. Physical condition and rate of deaths were monitored throughout the whole observation period. Mean body weight of each group were recorded immediately prior to dosing (control weights) and at 7 and 14 days. The results indicated a slight body weight gain in male rats during the whole concentration range. The body weight of female rats remained unchanged during the selected concentration range. No substance related gross changes were seen. Signs and symptoms like sedation, dyspnoea, ruffled fur, diarrhoea and curved body position were observed in animals treated with doses of 1000, 2000 and 3000 mg/kg of the test material. Animals treated with 5000 mg/kg of the test material showed additionally ventral and lateral body position. Mortality occurred in male and female rats.

The acute oral LD50 value of the test material was found to be 2900 mg/kg bw.

 

Supporting study

Three supporting studies were performed to determine the oral acute LD50 value of the test material. Both the test material which contained 95% of the active ingredient as well as the test material which is composed of 17% dye and 83% water were examined. Therefore, the different species (rat, chinese hamster) were treated orally, with a single dose, by means of a gavage. The following LD50 values were determined over a period of 14 days.

- Test material (17% act. ingr.): LD50 greater than 2500 mg/kg bw (rat)

- Test material (approx. 95% act. ingr.): LD50 is 4318 mg/kg bw (chinese hamster)

 

Disregarded study

An oral acute toxicity study was performed with mice. According to Regulation (EC) No 1272/2008 (annex I, part III), the preferred test species for evaluation of acute toxicity by the oral is the rat. All other acute oral toxicitiy study indicated a LD50 value greater than 2000 mg/kg bw. Thus, the oral acute toxicity study with mice is considered to be disregarded.

 

Acute dermal toxicity:

Key study

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 the test material (> 90% act. ingr.) as suspension in corn oil Ph.Eur. 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. Neither signs of systemic toxicity nor local skin effects were observed in the animals. Only test item residues on the application area were observed on study day 1. The mean body weight of the animals increased within the normal range throughout the study period with three exceptions in the female group. These females showed a stagnation of body weight within the first week, but body weights were within the normal range during the second week. Due to the fact that stagnation of body weight is commonly known for females dermally applied, this stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study (5 males/5 females). No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be greater than 2000 mg/kg bw in female and male rats.


Justification for selection of acute toxicity – oral endpoint
The study used the rat which is the preferred rodent species. The test material contained nearly 100% of the act. ingr.

Justification for selection of acute toxicity – dermal endpoint
One reliable study available which was perfomed under GLP/guideline conform conditions.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the test substance is not considered to be classified for acute oral toxicity or dermal toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation EC 605/2014.

Categories Display