Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From December 15, 2017 to March 20, 2018
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
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Rayttus norvegicus
Sex:
female
Details on test animals and environmental conditions:
- Source: Animais de Laboratorio Criacao e Comercio Ltda (ANILAB)
- Age at study initiation: 8-9 weeks old
- Housing: three animals per cage
- Water: ad libitum
- Acclimation period: 5 days
- Temperature (°C): 19.8-23.9 °C
- Humidity (%): 48-70 %
- Photoperiod (hrs dark / hrs light): 12-hrs dark / 12-hrs light cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Purified water
Doses:
300 and 2000 mg/kg B.W.
No. of animals per sex per dose:
Three

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.

Any other information on results incl. tables

Table 1.Individual body weight.

Treatment

Dose

(mg/kg)

Animal #

Body Weight (g)

Initial

(Day 0)

Day 7

Day 14

Difference between final and initial weight

1st

300

1

176.79

197.11

206.56

29.77

2

185.60

211.13

207.02

21.42

3

170.04

190.67

195.23

25.19

2nd

300

1

170.38

177.80

186.56

16.18

2

197.87

202.74

228.86

30.99

3

188.01

193.91

207.20

19.19

3rd

2000

1

240.02

243.32

247.20

7.18

2

233.32

233.09

241.25

7.93

3

235.54

239.52

247.43

11.89

4th

2000

1

231.11

241.76

156.10

24.99

2

208.10

212.56

218.39

10.29

3

207.68

222.42

229.42

21.74

Table 2. Behavioral and clinical alterations observed during the experimental period.

Treatment

Step

Sex

Animal#

Observation day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0:30h

10:00h

11:27h

12:06h

300

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Treatment

Step

Sex

Animal#

Observation day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0:30h

10:07h

12:00h

14:06h

300

2

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Treatment

Step

Sex

Animal#

Observation day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0:30h

11:15h

12:30h

14:10h

2000

3

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Treatment

Step

Sex

Animal#

Observation day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0:30h

11:27h

12:35h

14:02h

2000

4

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 - None visual alterations observed.

 

Table 3. Pathological findings in animals at doses of 300 and 2000 mg/kg of body weight.

Treatment

Dose

(mg/kg)

Anomal#

Macroscopic Alterations

Skin

Brain

Eyes

Lungs

Heart

Liver

Spleen

Urinary system

G.I.T

R.T

Carcass

1st

300

1

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

2nd

300

1

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

3rd

2000

1

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

4th

2000

1

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

G.I.T - Gastrointestinal tract

R.T - Reproductive tract

0 – Not observed alteration

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
According to OECD 423 test method, the oral LD50 value of Everzol SR98 was estimated to be 5000 mg/kg B.W. for female rats. Therefore, Everzol SR98 was Category 5 based on GHS criteria.

Executive summary:

This test using the procedures outlined in the BIOAGRI Study Plan for 16264.463.103.17. Twelve females, divided in groups of three animals, were tested in four steps at the dose levels of 300 and 2000 mg/kg B.W.. The test substance was applied diluted using purified water. The volume administered to each animal was calculated according to the body weight determined on the day of treatment. After dosing by gavage, the animals were observed during 14 days to evaluate deaths, and behavioral and clinical alterations. The test substance administered by oral route for female rats did not cause treatment-related deaths in any of the steps at the dose levels of 300 and 2000 mg/kg B.W.. At the clinical examinations, toxicity signs were not observed. The animals were euthanized in the end of the observation period and were submitted to necropsies, where they did not present macroscopic alterations or acute toxic effects caused by test substance. Based on the flow chart with the starting dose of 300 mg/kg B.W., the test substance was classified as category 5, according to the GHS. The acute oral LD50 value of the test substance Everzol SR98 was estimated to be 5000 mg/kg B.W. for female rats.