Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 275-965-6 | CAS number: 71735-74-5
Endpoint summary
Administrative data
Description of key information
In an acute oral toxicity study the oral LD50 was determined to be greater than 5000 mg/kg body weight. An acute dermal test with a structural analogue did not cause mortality upon single dermal application of 2000 mg/kg bw as tested in a GLP-compliant study following OECD testing guideline 402 (1987).
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:
- 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- non GLP, no bw developement, no necropsy, considered of minor importance due to absence of mortality and overt signs of toxicity
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- A pilot acute oral toxicity study carried out on groups of 4 young adult rats (2 male, 2 female) at dose levels of 2.5, 5 and 10 ml/kg, followed by an acute oral toxicity study carried out on a group of 10 young adult rats (5 female, 5 male) at a dose level of 5 ml/kg. The rats were weighed in groups of 2 or 5 and the average bodyweight used to calculate the volume administered.
- GLP compliance:
- no
- Test type:
- standard acute method
- Species:
- rat
- Strain:
- other: Sprague-Dawley derived rats of the C.D. strain
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (U.K. ) Limited, Margate, Kent, UK
- Weight at study initiation: 220-300g
- Housing: groups of 2 (pilot study) or 5 (main study) in plastic cages
- Diet: Oxoid Breeding Diet supplied by Herbert C. Styles (Bewdley) Limited, ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 +/- 1
- Humidity (%): 50-70 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A pilot acute oral toxicity study carried out on groups of 4 young adult rats (2 male, 2 female) at dose levels of 2.5, 5 and 10 mL/kg. 50% mortality was observed at the highest dose level (10 mL/kg) and no deaths at 2.5 and 5 ml/kg. - Doses:
- 2,5, 5 and 10ml/kg in the pre-test
5 mL/kg in the main test - No. of animals per sex per dose:
- 2 in the pre-test
5 in the main test - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Other examinations performed: The animals were observed for signs of toxicity at hourly intervals for the 8 hours following treatment and daily for the subsequent 14 days. - Preliminary study:
- In the pilot study 50% mortality was observed at the highest dose level (10 mL/kg). No deaths occurred in rats treated at 2.5 and 5mL/kg.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 mL/kg bw
- Mortality:
- 50% at 10 mL /kg in the pilot study.
- Clinical signs:
- other: The two animals dying in the pilot study were lethargic and adopted a hunched stance 24 hours after treatment which persisted until death. No overt signs of toxicity w ere observed in the surviving animals.
- Gross pathology:
- not performed
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral LD50 of the test substance is likely to be in excess of 5 ml/kg.
- Executive summary:
An acute toxicity test on Sprague Dawley rats was performed to assess the toxic potential of the test substance after oral ingestion. In a pilot study carried out on groups of 4 young adult rats (2 male, 2 female) at dose levels of 2.5, 5 and 10 ml/kg, 50% mortality was observed at the highest dose level. No deaths occurred in rats treated at 2.5 and 5 ml/kg. The following main study was performed with a group of 10 young adult rats (5 female, 5 male) at a dose level of 5ml/kg, in which no mortalities were reported. Bases on this result, the test article is considered to be practically non toxic after a single oral ingestion.
Reference
| Dose Level (mL/kg) | Animals | Average weight (g) | Volume dosed (mL) | Number surviving | ||||||||
| Pilot study |
day | 1 | 2 | 3 | 4 | 5 | 6 | 7 -14 | ||||
| 2.5 |
2 male | 300 | 0.75 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | ||
| 2 female | 250 | 0.63 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
|||
| 5 |
2 male | 250 | 1.25 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
||
| 2 female | 250 | 1.25 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
|||
| 10 |
2 male | 300 | 3 | 2 | 2 | 1 | 1 | 1 | 1 | 1 |
||
| 2 female | 220 | 2.2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 |
|||
| Main study | ||||||||||||
| 5 |
5 male | 250 | 1.25 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
||
| 5 female | 220 | 1.1 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
|||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 000 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
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- (1987)
- Deviations:
- no
- GLP compliance:
- yes
- 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
- Strain as stated in the report: HanIbm: WIST (SPF)
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllingsdorf / Switzerland
- Age at study initiation: males 9 weeks, females 12 weeks
- Weight at study initiation: males 233 - 253 g, females 203 - 224 g
- Housing:During acclimatisation 5 in Makrolon type-4 cages, during treatment and observation individually in Makrolon type-3 cages
- Diet: Pelleted standard Kliba 3433, rat maintenance diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: back of animals
- % coverage: 10 % of total body surface
- Type of wrap if used: semi-occlusive dressing fixed with an elastic adhesive bandage
REMOVAL OF TEST SUBSTANCE
- Washing: Skin was flushed with lukewarm tap water
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant concentration used: yes, 100 % of pure compound - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 males, 5 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 15 days
- Frequency of observations for mortality and clinical symptoms: 4-times on first day, afterwards once daily
- Frequency of weighing: On first day, day 8 and day 15
- Necropsy of survivors performed: yes, all animals were sacrified and subjected to gross pathology - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: None of the treated animals died. No clinical signs were observed.
- Mortality:
- No animal died.
- Clinical signs:
- other: No clinical signs were observed.
- Gross pathology:
- No macroscopic findings were observed at necropsy.
- Interpretation of results:
- GHS criteria not met
Reference
Body weight of male and female rats after single dermal treatment with 2000 mg/kg bw of test article
Body weight in grams: |
||||
Sex |
Animal No. |
Day of treatment |
Day 8 |
Day 15 |
male |
1 |
252.8 |
276.6 |
310.9 |
2 |
246.8 |
260.8 |
284.6 |
|
3 |
232.8 |
251.5 |
269.3 |
|
4 |
253.4 |
270.9 |
298.4 |
|
5 |
234.7 |
246.7 |
266.4 |
|
female |
6 |
210.3 |
218.3 |
223.9 |
7 |
202.7 |
203.1 |
212.3 |
|
8 |
211.5 |
215.7 |
227.7 |
|
9 |
223.7 |
223.5 |
234.7 |
|
10 |
205.7 |
208.3 |
214.7 |
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
Additional information
Acute oral toxicity
An acute pre-GLP toxicity study was performed with Sprague Dawley rats to assess the toxic potential of the test substance after single oral ingestion. In a pilot study the test item was administered once orally via gavage to groups of 4 young adult rats (2 male, 2 female) at dose levels of 2.5, 5 and 10 ml/kg. At the highest dose level 50% mortality was observed. No deaths occurred in rats treated with 2.5 and 5ml/kg. The following main study was performed with a group of 10 young adult rats (5 female, 5 male) at a dose level of 5 ml/kg; no mortalities and no clinical signs were reported. Based on this result, the test article is considered to be practically non toxic after a single oral ingestion and the LD50 is estimated to exceed 5000 mL/kg. Considering the density of the test substance the adjusted LD50 value is greater than 5000 mg/kg body weight.
Acute dermal toxicity
Acute dermal toxicity data is taken from a structural analogue (see attached read across justification). Here, a group of five male and five female Hanlbm: WIST (SPF) rats was treated at 2000 mg/kg bw by dermal application. The test article was applied undiluted. The animals were examined for clinical signs four times during day 1 and once daily during days 2-15. Mortality was recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age.
Acute inhalation toxicity
no data available
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
