Registration Dossier

Administrative data

Description of key information

Not found to be hazardous by ingestion or in contact with skin

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Testing carried out in accordance to: OECD Guideline for testing of Chemicals (No. 401. Acute Oral Toxicity, Feb, 1987) State Environmental Protection Administration: The Guidelines for the Testing of Chemicals Ministry of Health, 2005: Technical Standards for testing of chemicals
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: State environmental protection administration: the guidelines for the testing of chemicals
Deviations:
no
Qualifier:
according to
Guideline:
other: Ministry of health 2005: Technical standards for testing of chemicals
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
other: NIH
Sex:
male/female
Details on test animals and environmental conditions:
Test species: Mice.
Strain: NIH.
Supplier: Guangdong Medical Laboratory Animal Center [certified animal number SCXK (Guangdong) 2008-0002].
Number of animals: 10 males and 10 females.
Number of groups: 2(test group and solvent control group).
Number of animal/group: 5 males and 5 females per group.
Body weight at the start of experiment: 22.4 ~ 32.3g .
Identification of animals: Tags marked with animal group number and treatment details were attached to cages. Each animal was given a unique number.
Acclimatization: Five days prior to the experiment in the test room.
Randomization: Animals were assigned to two groups.

Environmental conditions
Test Room: SPF animal lab in the Center
Animal house conditions: The test facility was an air-conditioned room with 12h artificial fluorescent light and 12h dark.
Temperature range: 20~25oC.
Humidity range: 40~70%.

Husbandry Practices
Caging: Stainless steel cages were used. Autoclaved clean dry corncob was used as the bedding material. Animals were housed in one group according to sex in cages.
Water bottle: Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
Sanitation: Bedding material was changed daily.
Food and water: Standard pellet feed supplied by Guangdong Medical Laboratory Animal Center and ultra-pure filtered sterilized water were provided to the animals freely.
Frequency of providing feed and drinking water: Both drinking water and feed were provided ad libitum.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Preparation of test substance: Known weights of the test substance were mixed with distilled water, and thereafter administered to groups of mice at the desired dose levels.
Doses:
Administration: All mice were fasted overnight prior to administration on of the test substance. The tested animals (5 males and 5 females each group) were given Pepton 22 ,which was dissolved in distilled water, by gavages at the dose of 5050 mg/kg and at the volume of 10ml/kg for once; Animals of solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group.

Dose levels: A limit test at one dose level of 5050 mg/kg was carried out with mice (5 males and 5 females); the solvent control group was given distilled water instead of tested compounds was carried out with mice (5 males and 5 females) too.
No. of animals per sex per dose:
Number of animals: 5 males and 5 females per group.
Control animals:
yes
Details on study design:
Acute oral toxicity of Pepton 22 was tested in two groups of mice. The tested animals (5 males and 5 females each group) were given Pepton 22 ,which was dissolved in distilled water, by gavages at the dose of 5050 mg/kg and at the volume of 10ml/kg for once; Animals of solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group. Mice were observed for 14 days after the exposure. At the end of the test, all survivals were weighed and sacrificed, and necropsy were carried out. Body weight of the animals were recorded before and weekly after exposure.

Observation period: All animals were observed individually, daily for 14 days for various end-points of toxicity.

Body weight: Body weight of each animal was recorded just prior to administration of dose (0 day) and on day 7 and day 14 following the dosing.

Mortality: All animals were observed for mortality daily throughout the observation period.

Toxicity: All animals were observed for toxicity signs soon after dosing and once daily throughout the observation period until day 14 when the experiment was terminated.

Necropsy: Survivors were necropsied at the end of 14-day observation period for gross pathological examination. Autopsy was carried out in animals died during the observation period.
Preliminary study:
Acute oral LD50 of Pepton 22 (supplied by Thomas Swan & Co. Ltd.) was greater than 5050 mg/kg both in female and male NIH mice.
Based on Globally Harmonized System of classification and Labelling of Chemicals (GHS), Pepton 22 was classified as category 5. Referring to “Acute oral, inhalation, dermal toxicity grading” of “The guidelines for the hazard evaluation of new chemical substance” (HJ/T 154-2004), State Environmental Protection Administration, Pepton 22 was “Actually Nontoxic”.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 050 mg/kg bw
Mortality:
Result of the acute oral toxicity test on Pepton 22, no mortality was observed in the treated group of mice throughout the observation period (Table 1).
Clinical signs:
In the dose level of 5050 mg/kg, all the animals were no abnormalities detected except slight inactivity. There was no mortality observed in mice treated with the test substance throughout the observation period.
Body weight:
The appreciable change in body weight gain was observed in the test substance treated mice (Table2, Table 3).
Gross pathology:
No gross abnormalities were seen in the group of animals at necropsy at the end of 14-day observation period (Table 4).

Mortality Data and LD50

Table 1

Groups

 

Female

 

Male

 

Animal number of each group

Dead animals

 

Animal number of each group

Dead animals

5050mg/kg

 

5

0

 

5

0

solvent control

 

5

0

 

5

0

LD50(95CI)

 

5050mg/kg(not elicited)

 

5050mg/kg(not elicited )

 

Body weight

Table 2

Groups

Gender

No.

0d

7d

14d

weights

weights

weights

5050

mg/kg

1      

23.9

23.9

28.3

4      

26.0

27.0

34.1

5      

26.4

26.4

32.5

6      

24.6

26.0

33.0

8      

25.9

28.7

35.2

1      

28.8

32.8

40.4

4      

30.0

37.5

43.6

7      

30.1

34.1

41.7

9      

32.7

37.4

44.0

10     

29.2

34.6

39.7

solvent control

2      

26.2

27.4

32.3

3      

25.3

28.4

34.0

7      

26.1

27.4

33.5

9      

22.4

23.7

29.7

10     

25.9

29.2

34.5

2      

31.0

40.3

45.1

3      

29.3

36.1

42.0

5      

29.2

34.0

39.8

6      

28.0

32.6

39.1

8      

32.3

39.2

46.3

 

 

 

 

Table 3

Groups

Gender

0d

7d

14d

5050mg/kg

Female

25.4±1.15

26.4±1.75

32.6±2.65

Male

30.2±1.55

35.3±2.15

41.9±1.95

solvent control

Female

25.2±1.65

27.2±2.15

32.8±1.95

Male

30.0±1.75

36.4±3.35

42.5±3.25

 

Gross pathology data

Table 4

Groups

Gender

No.

Lesions

Groups

Gender

No.

Lesions

5050mg/kg

1      

NAD

solvent control

2      

NAD

4      

NAD

3      

NAD

5      

NAD

7      

NAD

6      

NAD

9      

NAD

8      

NAD

10     

NAD

1      

NAD

2      

NAD

4      

NAD

3      

NAD

7      

NAD

5      

NAD

9      

NAD

6      

NAD

10     

NAD

8      

   NAD

 

NAD – no abnormalities detected

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Data shows that material is not classified according to REGULATION (EC) No 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
5 050 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Testing carried out in accordance to: OECD Guideline for Testing of Chemicals No. 402. Acute Dermal Toxicity, Feb. 1987 State Environmental Protection Administration : The Guidelines for the Testing of Chemicals Ministry of Health, 2005: Technical standards for testing of chemicals .
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: State Environmental Protection Administration : The Guidelines for the Testing of Chemicals
Deviations:
no
Qualifier:
according to
Guideline:
other: Ministry of Health, 2005: Technical standards for testing of chemicals
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Test species: Rats.
Strain: SD.
Supplier: Guangdong Medical Laboratory Animal Center [certified animal number SCXK (Guangdong) 2008-0002].
Number of animals: 10 males and 10 females.
Number of groups: 2(test group and solvent control group).
Number of animal/group: 5 males and 5 females per group.
Body weight at the start of experiment: 197 ~ 274g .
Identification of animals: Tags marked with animal group number and treatment details were attached to cages. Each animal was given a unique number.
Acclimatization: Five days prior to the experiment in the test room.
Randomization: Animals were assigned to two groups.

Environmental conditions
Test Room: SPF animal lab in the Center
Animal house conditions: The test facility was an air-conditioned room with 12h artificial fluorescent light and 12h dark.
Temperature range: 20~25oC.
Humidity range: 40~70%.

Husbandry Practices
Caging: Stainless steel cages were used. Autoclaved clean dry corncob was used as the bedding material. Animals were housed in one group according to sex in cages.
Water bottle: Each cage was supplied with a polypropylene water bottle with a stainless steel nozzle.
Sanitation: Bedding material was changed daily.
Food and water: Standard pellet feed supplied by Guangdong Medical Laboratory Animal Center and ultra-pure filtered sterilized water were provided to the animals freely.
Frequency of providing feed and drinking water: Both drinking water and feed were provided ad libitum.
Type of coverage:
open
Vehicle:
water
Details on dermal exposure:
Test Procedure: An area of about 5×8 cm2 on the back of the animal was clipped free of hair. 24h later, the intact animals were selected to use. Pepton 22 was administered on the hair-free site of the rats. The rats were fasten in the stainless steel shelves for 24h, then the test site were cleaned with warm water. Animals of the test group were conducted in the 2500 mg/kg dose limit test, the solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group.
Control animals:
yes
Details on study design:
Acute dermal toxicity of Pepton 22 (supplied by Thomas Swan & Co. Ltd.) was tested in two groups of Rats. Pepton 22 was administered on the hair-free site of the rats. The rats were fasten in the stainless steel shelves for 24h, then the test site were cleaned with warm water. Animals of the test group were conducted in the 2500 mg/kg dose limit test, the solvent control group were given distilled water instead of tested compounds, with the same procedure as the test group. Rats were observed for 14 days after the exposure. At the end of the test, all survivals were weighed and sacrificed, and necropsy were carried out. Body weight of the animals was recorded before and weekly after exposure.
Preliminary study:
Acute dermal LD50 of Pepton 22 (supplied by Thomas Swan & Co. Ltd.) was greater than 2500 mg/kg both in female and male SD rats.
Based on Based on Globally Harmonized System of classification and Labelling of Chemicals (GHS), Pepton 22 was classified as category 5. According to “Acute oral、inhalation、dermal toxicity grading” of “The guidelines for the hazard evaluation of new chemical substance” (HJ/T 154-2004), State Environmental Protection Administration, Pepton 22 was “Actually Nontoxic”.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Mortality:
Result of the acute dermal toxicity test on Pepton 22, no mortality was observed in treated group of rats throughout the observation period (Table 1).
Clinical signs:
In the dose level of 2500 mg/kg, all the animals were no abnormalities detected except slight inactivity. There was no mortality observed in rats treated with the test substance throughout the observation period.
Body weight:
The appreciable change in body weight gain was observed in the test substance treated rats (Table2, Table 3).
Gross pathology:
No gross abnormalities were seen in the group of animals at necropsy at the end of 14-day observation period (Table 4).

Mortality Data and LD50

Table 1

Groups

 

Female

 

Male

 

Animal number of each group

Dead animals

 

Animal number of each group

Dead animals

2500mg/kg

 

5

0

 

5

0

 

solvent control

 

5

0

 

5

0

 

LD50(95%CI)

 

>2500mg/kg(not elicited)

 

>2500mg/kg(not elicited )

 

 

Body weight

Table 2

Groups

Gender

No.

0d

7d

14d

weights

weights

weights

2500

mg/kg

1      

203

235

254

3      

197

218

238

7      

214

234

262

8      

211

229

254

12     

204

231

250

2      

257

292

337

3      

270

309

347

4      

267

300

347

7      

257

306

344

12     

241

284

330

solvent control

2      

201

221

239

4      

207

233

258

5      

207

231

265

9      

202

202

246

10     

224

245

273

1      

265

313

346

5      

274

318

368

8      

262

315

359

9      

252

306

362

10     

255

297

353

 

 

 

 

 

 

Table 3

Groups

Gender

0d

7d

14d

2500mg/kg

Female

205.8±6.8 (5)

229.4±6.8 (5)

251.6±8.8  (5)

Male

258.4±11.3 (5)

298.2±10.2 (5)

341.0±7.4 (5)

solvent control

Female

208.2±9.2 (5)

226.4±16.1 (5)

256.2±13.8 (5)

Male

261.6±8.7 (5)

309.8±8.4 (5)

357.6±8.4 (5)

 

Gross pathology data

Table 4

Groups

Gender

No.

Lesions

Groups

Gender

No.

Lesions

2500 mg/kg

1      

NAD

solvent control

2      

NAD

4      

NAD

3      

NAD

5      

NAD

7      

NAD

6      

NAD

9      

NAD

8      

NAD

10     

NAD

1      

NAD

2      

NAD

4      

NAD

3      

NAD

7      

NAD

5      

NAD

9      

NAD

6      

NAD

10     

NAD

8      

    NAD

 

NAD – no abnormalities detected

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Data shows that material is not classified according to REGULATION (EC) No 1272/2008
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 500 mg/kg bw

Additional information

Acute toxicity: oral mouse = >5050 mg/kg Dermal Rat = >2500 mg/kg Inhalation not performed as exposure unlikely

Justification for classification or non-classification