Registration Dossier

Administrative data

Description of key information

Oral:

Three in vivo tests are available.

Key study:

The study to investigate acute oral toxicity of the test item, was conducted on female Sprague-Dawley (SD) rats in compliance with OECD 423 and GLP. The LD50 was determined to be > 2000 mg/kg body weight.

Supporting study:

The acute oral toxicity to Sprangue-Dawley rats were determined by the acute digestive tract route in accordance with GB/T 21603-2008 Chemicals-Test method of acute oral toxicity (similar to OECD 401). The acute oral LD50 of test item were 1710 mg/kg and 2330 mg/kg for female and male rats separately. No table for general findings and necropsy is shown and also no certificate for the test substance is included.

An acute oral toxicity test was conducted with fixed dosed method (similar to OECD 420). All 5 female animals were dosed at the same time. The LD50 was determined to be > 2000 mg/kg bw.

 

Inhalation: No study available

 

Dermal:

The acute dermal toxicity of the test substance to SD rats was determined in accordance with GB/T 21606-2008 Chemicals-Test method of acute dermal toxicity (similar to OECD 402). The acute dermal LD50 of the test substance for male and female rats was estimated to be over 2000 mg/kg.

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:
supporting study
Study period:
From 2014-10-15 to 2014-12-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: GB/T 21603-2008 Chemicals-Test method of acute oral toxicity
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No table for general findings and necropsy is shown and also no certificate for the test substance is included
GLP compliance:
no
Remarks:
authorized by CNAS
Limit test:
no
Specific details on test material used for the study:
- Purity: 100.0%
- Lot No.: KNC110310
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Slac Jingda Laboratory Animal Co., Ltd, Hunan Province.
- Weight at study initiation: 189 ~ 220 g
- Fasting period before study: Food but not water was withheld overnight to rats
- Housing: housed in SPF Barrier environment
- Diet: All of the feeds were supplied by Tianqin biotechnology Ltd., Changsha
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ~ 22
- Humidity (%): 56-69
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
- Test solution preparation:
An amount of test item was grinded and then diluted into required concentration 46.4 mg/mL, 100 mg/mL, 215 mg/mL and 232 mg/mL for the test with 1% methylcellulose solution.

- Administration:
The dosing liquids were administered orally to rats by gavage for 1.0 mL/100 g BW (except 4640 mg/kg group for 2.0 mL/100 g BW).
Doses:
464 mg/kg, 1000 mg/kg, 2150 mg/kg and 4640 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical/behavioral signs of toxicity were recorded daily thereafter for 14 days. Body weights were recorded at Day 0, 7, and 14.
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 710 mg/kg bw
Based on:
test mat.
95% CL:
> 1 260 - < 2 330
Sex:
male
Dose descriptor:
LD50
Effect level:
2 330 mg/kg bw
Based on:
test mat.
95% CL:
> 1 600 - < 3 390
Mortality:
All of the animals in the high dose group died during the time of 2-24 h after administration. The animals in the second high dose group died during the time of 6 - 24 h and the survival animals recovered in the time of the fourth day after administration. No death occurred during the 14 days in the low and medium dose groups.
Clinical signs:
The animals in the second high dose group and high dose group were lack of movement in the time of 30 minutes after administration. Clothing hair fluffiness and bad of mental status were observed later. The animals in the medium dose group were lack of movement in the time of 6 hours and recovered in the time of 24 hours after administration. No detectable clinical signs occurred in any test animal of low dose group.
Body weight:
Individual body weights increased at the 7th and 14th day after dosing.
Gross pathology:
No abnormal necropsy findings occurred in any dead animal. No abnormal necropsy findings occurred in any animal of low and medium dose groups.
Interpretation of results:
study cannot be used for classification
Conclusions:
The acute oral LD50 of test item were 1710 mg/kg and 2330 mg/kg for female and male rats separately.
Executive summary:

The acute oral median lethal dose and the health hazards of the test substance to Sprangue-Dawley rats were determined by the acute digestive tract route in accordance with GB/T 21603-2008 Chemicals-Test method of acute oral toxicity. Four dose groups (5 males and 5 females each group) were used. The dose levels were 464 mg/kg, 1000 mg/kg, 2150 mg/kg and 4640 mg/kg.

The animals in the second high dose group and high dose group were lack of movement in the time of 30 minutes after administration. Clothing hair fluffiness and bad of mental status were observed later. The animals in the medium dose group were lack of movement in the time of 6 hours and recovered in the time of 24 hours after administration. No detectable clinical signs occurred in any test animal of low dose group. No abnormal necropsy findings occurred in any dead animal. No abnormal necropsy findings occurred in any animal of low and medium dose groups. Individual body weights increased at the 7th and 14th day after dosing.

The acute oral LD50 of test item were 1710 mg/kg and 2330 mg/kg for female and male rats separately.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
1 (reliable without restriction)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Clinical signs:
other:
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:
From 2014-12-01 to 2014-12-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: GB/T 21606-2008 Chemicals-Test method of acute dermal toxicity
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
authorized by CNAS
Limit test:
yes
Specific details on test material used for the study:
- Purity: 100.0%
- Lot No.: KNC110310
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Slac Jingda Laboratory Animal Co., Ltd, Hunan Province
- Weight at study initiation: 208 ~ 232 g
- Housing: housed in SPF Barrier environment
- Diet: AII ofthe feeds were supplied by Tianqin biotechnology Ltd, Changsha
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 56-69
Type of coverage:
occlusive
Vehicle:
methylcellulose
Details on dermal exposure:
About 4 cm x 5 cm areas of fur was clipped from the rats' back at 24 h before dosing. An amount of test item was grinded and then diluted into required concentration 500 mg/mL for the test with 1 % methylcellulose solution. The dosing Iiquids was equably applied to the smooth area (approximately 10 percent of the body surface area) of the rats in a single dose (0.4 mL/100 g BW) . The area of application was covered with a 2 ply in surgical gauze patch and secured in non-irritating adhesive tape.
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 femles and 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical/behavioral signs of toxicity were made daily thereafter for 14 days. Body weights were records at Day 0, 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the 14 days
Clinical signs:
No detectable clinical signs occurred in any test animals during the 14 days.
Body weight:
Individual body weights increased at the 7th and 14th day after dosing.
Gross pathology:
No abnormal necropsy findings occurred in any test animal.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of the test substance for male and female rats was estimated to be over 2000 mg/kg.
Executive summary:

The acute dermal median lethal dose and the health hazards of the test substance to SD rats were determined in accordance with GB/T 21606-2008 Chemicals-Test method of acute dermal toxicity. One single dose of 2000 mg/kg was chosen.

No detectable clinical signs occurred in any test animals, and no death occurred during the 14 days. Individual body weights increased at the 7th and 14th day after dosing. No abnormal necropsy findings occurred in any test animal.

The acute dermal LD50 of the test substance for male and female rats was estimated to be over 2000 mg/kg.  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
1 (reliable without restriction)

Additional information

Justification for classification or non-classification

Acute toxicity:

Oral:

Acute oral toxicity test, OECD 423, GLP, Korean lab: LD50: > 2000 mg/kg body weight for female.

Acute oral toxicity test, similar to OECD 401, China lab: LD50:1710 mg/kg for female and 2330 mg/kg for male rats.

Acute oral toxicity test, similar to OECD 420: LD50 > 2000 mg/kg bw for female 

The China lab cannot be used as key study because it is reliable with restriction as no table for general findings and necropsy is shown and also no certificate for the test substance is included. And the study report of the Korean lab is used as a key report and used for classification by refer LD50 value (>2000 mg/kg for female) in the report.

 

Dermal:

Acute dermal test, similar to OECD 402: LD50 >2000 mg/kg.

 

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1, this substance should be not classified for acute oral and dermal toxicity.

 

Specific target organ toxicity-single exposure:

Oral:

Acute oral toxicity test, OECD 423:

Mortality: 1 animal (on day 1) at 2000 mg/kg B.W. died.

Clinical observations: no clinical signs caused by administration of the test substance.

Necropsy: Dead animal, hemorrhage in around mouth in external finding was observed. Surviving animals: no abnormal findings

Acute oral toxicity test, similar to OECD 401:

Mortality: All animal died in high dose group (10/10) and 4 females and 2 males died in the second high dose group

Clinical observations: The animals in the second high dose group and high dose group were lack of movement in the time of 30 minutes after administration. Clothing hair fluffiness and bad of mental status were observed later. The animals in the medium dose group were lack of movement in the time of 6 hours and recovered in the time of 24 hours after administration. No detectable clinical signs occurred in any test animal of low dose group.

Necropsy: No abnormal necropsy findings occurred in any dead animal. No abnormal necropsy findings occurred in any animal of low and medium dose groups.

Acute oral toxicity test, similar to OECD 420:

Mortality: No mortality occurred

Clinical observations: Irregular respiration was observed in 1/5 rats 30 min after dosing, and in 4/5 rats 1-4 h after administration. A decrease of spontaneous activity was also noted in 1/5 animals 30 min after dosing, increasing to 2-3/5 animals 1-4 h after administration. Muscular rigidity was noted in 2-5 rats, in an increasing number from 1 to 4 h after administration. Stains around the eyes and snout were observed in all 5 animals on Day 1, persisting until Day 2 in 1/5, while stains around the mouth was observed in 3/5 Day 1. Clonic convulsion were noted in 1/5 rats 4h after dosing. Urinary incontinence were noted in 1/5 rats during Day 1. No clinical signs were observed from Day 3 onward.

Necropsy: No substance-related findings were noted

 

Dermal:

Acute dermal test, similar to OECD 402:

Mortality: No death occurred

Clinical observations: No detectable clinical signs occurred in any test animals

Necropsy: No abnormal necropsy findings occurred in any test animal

 

In accordance with Regulation (EC) No. 1272/2008 section 3.8.2.1.7., the effects observed are not considered as adverse effects that support classification, therefore this substance should be not classified.