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EC number: 812-957-9 | CAS number: 333350-60-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
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- Boiling point
- Density
- Particle size distribution (Granulometry)
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
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- Toxicological Summary
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- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (LD50 cut-off: 500 mg/kg body weight, Globally Harmonized Classification System: Category 4, >300 - 2000 mg/kg body weight).
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016 - 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Animal Information
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously dosed animals.
Animal Care and Husbandry
The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study. - Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on oral exposure:
- All animals were dosed once only by gavage
- Doses:
- 300 mg/kg
2000 mg/kg - No. of animals per sex per dose:
- 3 females per dose, 3 dose groups
- Control animals:
- no
- Details on study design:
- In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Groups of fasted animals were treated as follows:
Dose Level(mg/kg) Concentration(mg/mL) Dose Volume(mL/kg) Number of Rats(Female)
300, 30, 10, 3
2000, 200, 10, 3
300, 200, 10, 3
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained. - Statistics:
- None recorded.
- Preliminary study:
- Not applicable.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- ca. 500 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 95% CL not reported
- Mortality:
- All animals treated at a dose level of 2000 mg/kg were killed for humane reasons, 4 hours after dosing, due to the occurrence of clinical signs of toxicity that reached the severity limit set forth in the UK Home Office Project Licence.
There were no deaths noted at a dose level of 300 mg/kg. - Clinical signs:
- other: Signs of systemic toxicity noted at a dose level of 2000 mg/kg were ataxia, hunched posture, lethargy, tiptoe gait, decreased and increased respiratory rate, labored respiration, ptosis, occasional body tremors and prostration. Hunched posture was noted
- Gross pathology:
- Abnormalities noted at necropsy of animals treated at a dose level of 2000 mg/kg were patchy pallor of the liver, white substance present in the stomach and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach.
No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg. - Other findings:
- None
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (LD50 cut-off: 500 mg/kg body weight, Globally Harmonized Classification System: Category 4, >300 - 2000 mg/kg body weight).
- Executive summary:
Introduction
The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.
Methods
A group of three fasted females was treated with the test item at a dose level of 300 mg/kg body weight. Based on the results from this dose level, further groups of fasted females were treated at dose levels of 2000 and 300mg/kg body weight. Dosing was performed sequentially.
The test item was administered orally as a suspension in arachis oil BP. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.
Results
Mortality. Allanimals treated at a dose level of 2000 mg/kg were killed for humane reasons, 4 hours after dosing, due to the occurrence of clinical signs of toxicity that reached the severity limit set forth in the UK Home Office Project Licence. There were no deaths noted at a dose level of 300 mg/kg.
Clinical Observations. Signs of systemic toxicity noted at a dose level of 2000 mg/kg were ataxia, hunched posture, lethargy, tiptoe gait, decreased and increased respiratory rate, labored respiration, ptosis, occasional body tremors and prostration. Signs of systemic toxicity noted at a dose level of 300 mg/kg were hunched posture, ataxia and lethargy. All animals treated at a dose level of 300 mg/kg appeared normal 1 day after dosing.
Body Weight. Surviving animals showed expected gains in body weight.
Necropsy. Abnormalities noted at necropsy of animals treated at a dose level of 2000 mg/kg were patchy pallor of the liver, white substance present in the stomach and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.
Conclusion
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (LD50 cut-off: 500 mg/kg body weight, Globally Harmonized Classification System: Category 4, >300 - 2000 mg/kg body weight).
Reference
Appendix1 Mortality Data
|
|
|
Deaths |
During |
Day of |
Dosing |
Deaths |
During |
Period |
After |
Dosing |
(Days) |
|
|
|
Dose Level mg/kg |
Sex |
Number of Animals Treated |
½ |
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8-14 |
Deaths |
300 |
Female |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0/3 |
|
Female |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0/3 |
2000 |
Female |
3 |
0 |
0 |
0 |
0 |
3* |
|
|
|
|
|
|
|
3/3 |
*= All animals killed for humane reasons due to the occurrence of clinical signs of toxicity that reached the severity limit set forth in the UK Home Office Project Licence
Appendix2 Individual Clinical Observations -300 mg/kg
|
|
Effects |
Noted |
After |
Dosing |
Effects |
Noted |
During |
Period |
After |
Dosing |
(Days) |
|
|
|
|
|
|
|
Dose Level mg/kg |
Animal Number and Sex |
½ |
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
300 |
1-0 Female |
H |
H |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-1 Female |
H |
H |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-2 Female |
H |
H |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-0 Female |
H |
HLA |
HLA |
HLA |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-1 Female |
H |
HLA |
HLA |
HLA |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-2 Female |
HA |
HLA |
HLA |
HLA |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0= No signs of systemic toxicity
A = Ataxia
H = Hunched posture
L = Lethargy
Appendix3 Individual Clinical Observations -2000 mg/kg
|
|
Effects Noted |
During Period |
After Dosing |
|
Dose Level mg/kg |
Animal Number and Sex |
30 Minutes |
1 Hour |
2 Hours |
4 Hours |
2000 |
2-0 Female |
HA |
HWt |
HLWtRi |
RdRlPtPrToX* |
|
2-1 Female |
HA |
HWt |
HLWtRi |
RdRlPtPrToX* |
|
2-2 Female |
HA |
HWt |
HLWtRi |
RdRlPtPrToX* |
A= Ataxia
H = Hunched posture
L = Lethargy
Pr = Prostration
Pt = Ptosis
Rd =Decreased respiratory rate
Ri = Increased respiratory rate
Rl = Labored respiration
To =Occasional body tremors
Wt =Tiptoe gait
X* =Animals killed for humane reasons due to the occurrence of clinical signs of toxicity that reached the severity limit set forth in the UK Home Office Project Licence
Appendix4 Individual Body Weights and Body Weight Changes -300 mg/kg
|
|
Body |
Weight (g) |
at Day |
Body Weight Gain (g) |
During Week |
|
Dose Level |
Animal Number |
0 |
7 |
14 |
1 |
2 |
|
300 |
1-0 Female |
162 |
178 |
198 |
16 |
20 |
|
|
1-1 Female |
166 |
179 |
187 |
13 |
8 |
|
|
1-2 Female |
164 |
172 |
188 |
8 |
16 |
|
|
3-0 Female |
188 |
207 |
221 |
19 |
14 |
|
|
3-1 Female |
163 |
182 |
196 |
19 |
14 |
|
|
3-2 Female |
179 |
194 |
214 |
15 |
20 |
Appendix5 Individual Body Weights and Body Weight Changes -2000 mg/kg
|
|
Body |
Weight (g) |
at Day |
Body Weight (g) |
Body Weight Gain (g) |
During Week |
Dose Level mg/kg |
Animal Number and Sex |
0 |
7 |
14 |
at Death |
1 |
2 |
2000 |
2-0 Female |
166 |
- |
- |
163 |
- |
- |
|
2-1 Female |
159 |
- |
- |
158 |
- |
- |
|
2-2 Female |
169 |
- |
- |
164 |
- |
- |
Appendix6 Individual Necropsy Findings-300 mg/kg
Dose Level |
Animal Number |
Time of Death |
Macroscopic Observations |
300 |
1-0 Female |
Killed Day 14 |
No abnormalities detected |
|
1-1 Female |
Killed Day 14 |
No abnormalities detected |
|
1-2 Female |
Killed Day 14 |
No abnormalities detected |
|
3-0 Female |
Killed Day 14 |
No abnormalities detected |
|
3-1 Female |
Killed Day 14 |
No abnormalities detected |
|
3-2 Female |
Killed Day 14 |
No abnormalities detected |
Appendix7 Individual Necropsy Findings -2000 mg/kg
Dose Level |
Animal Number |
Time of Death |
Macroscopic Observations |
2000 |
2-0 Female |
Humanely killed Day 0 |
Liver: patchy pallor Stomach: white substance present Gastric mucosa: epithelial sloughing Non-glandular epithelium of the stomach: epithelial sloughing |
|
2-1 Female |
Humanely killed Day 0 |
Liver: patchy pallor Stomach: white substance present Gastric mucosa: epithelial sloughing Non-glandular epithelium of the stomach: epithelial sloughing |
|
2-2 Female |
Humanely killed Day 0 |
Liver: patchy pallor Stomach: white substance present Gastric mucosa: epithelial sloughing Non-glandular epithelium of the stomach: epithelial sloughing |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 500 mg/kg bw
- Quality of whole database:
- reliable witout restriction
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
Category 4
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was approximately 500 mg/kg body weight (LD50 cut-off: 500 mg/kg body weight, Globally Harmonized Classification System: Category 4, >300 - 2000 mg/kg body weight).
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