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EC number: 904-908-6 | CAS number: -
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From May 9th, 2018 to May 29th, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- December 2001
- 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
Test material
- Reference substance name:
- Reaction Mass of Isoamyl salicylate and 2-Methylbutyl salicylate
- IUPAC Name:
- Reaction Mass of Isoamyl salicylate and 2-Methylbutyl salicylate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: JANVIER LABS (53940 Legenest St. Isle - France)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 213 ± 16.3 g
- Fasting period before study: overnight.
- Housing: Groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air-conditioned animal husbandry.
- Diet (e.g. ad libitum): Foodstuff (ENVIGO -2016) ad libitum.
- Water (e.g. ad libitum): Tap-water from public distribution system ad libitum. Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas- Eurofins (France).
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): 30-70%
- Air changes (per hr): 10 changes/hour
- Photoperiod (hrs dark / hrs light): 12 h light (7 - 19 h) / 12 h darkness
IN-LIFE DATES: From March 7th, 2018 To May 23rd, 2018
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 2.39 mL/kg (test item), 10 mL/kg (control).
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no indication of toxicity based on available data. Therefore, the selected starting dose was 2000 mg/kg body weight. - Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 6
- Control animals:
- yes
- Remarks:
- Study No. TAO423-2018-001 (see "Other information on results").
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systemic observations at 30 min, 1h, 3h, 4h, 24h, 48h
after administration and daily for 14 days. Weighing: on day 0 (just before administering the test item) then on Day 2, Day 7, and Day 14.
- Necropsy of survivors performed: yes. At termination, macroscopic observations were performed. Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Parameters examined: Oesophagus, Stomach, Duodenum, Jejunum, Ileum, Caecum, Colon, Rectum, Spleen, Liver, Thymus, Trachea, Lungs, Heart, Kidneys, Urinary Bladder, Ovaries, Uterus, Treatment Area, Adrenals and Pancreas.
- Other examinations performed: Clinical signs: Spontaneous activity, Preyer's reflex (noise), Respiratory rate, Convulsions, Tremors, Body temperature, Muscle tone, Palpebral opening, Pupil appearance, Salivation, Lachrymation, Righting reflex, Back hair appearance, Mortality.
Results and discussion
Effect levels
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality occurred during the study.
- Clinical signs:
- other: A decrease of spontaneous activity (6/6), muscle tone (5/6) and righting reflex (5/6) was noted a t30 minutes post dose. The animals recovered normal activity at 24 hours post dose.
- Gross pathology:
- The macroscopic examination of the animals at the end of the study did not reveal treatment-related changes.
Any other information on results incl. tables
Table 1. Test item at 2000 mg/kg bw. Body weight and weight gain in grams.
FEMALES |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
Rf 2488 Rf 2489 Rf 2490 |
191 200 196 |
225 220 210 |
24 20 14 |
238 249 247 |
47 49 51 |
250 270 265 |
59 70 69 |
Rf 2532 Rf 2533 Rf 2534 |
224 236 211 |
243 250 228 |
19 14 17 |
256 267 238 |
32 31 27 |
271 282 249 |
47 46 38 |
MEAN |
209.7 |
229.3 |
19.7 |
249.2 |
39.5 |
264.5 |
54.8 |
Standard deviation |
17.5 |
14.8 |
7.4 |
11.1 |
10.6 |
12.9 |
13.2 |
Table 2. Clinical signs
OBSERVATIONS: |
FEMALES |
FEMALES |
||||
T0 + 30 minutes |
Rf 2488 |
Rf 2489 |
Rf 2490 |
Rf 2532 |
Rf 2533 |
Rf 2534 |
Spontaneous activity |
D |
D |
D |
D |
D |
D |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
Muscle tone |
D |
D |
D |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
Righting reflex |
D |
D |
D |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||
OBSERVATIONS: |
FEMALES |
FEMALES |
||||
T0 + 1 hour |
Rf 2488 |
Rf 2489 |
Rf 2490 |
Rf 2532 |
Rf 2533 |
Rf 2534 |
Spontaneous activity |
D |
D |
D |
N |
D |
D |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||
OBSERVATIONS: |
FEMALES |
FEMALES |
||||
T0 + 3 hours T0 + 4 hours |
Rf 2488 |
Rf 2489 |
Rf 2490 |
Rf 2532 |
Rf 2533 |
Rf2534 |
Spontaneous activity |
D |
D |
D |
N |
D |
D |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
D |
D |
Palpebral opening |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
D |
D |
Back hair appearance |
N |
N |
N |
N |
N |
N |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||
OBSERVATIONS: |
FEMALES |
FEMALES |
||||
D1 to D14 |
Rf 2488 |
Rf 2489 |
Rf 2490 |
Rf 2532 |
Rf 2533 |
Rf 2534 |
Spontaneous activity |
N |
N |
N |
N |
N |
N |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
Convulsions |
N |
N |
N |
N |
N |
N |
Tremors |
N |
N |
N |
N |
N |
N |
Body temperature |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
MORTALITY |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||
Table 3. Necropsy findings
Found dead: GENERAL APPEARANCE |
|
Euthanasia BEFORE AUTOPSY:Normal |
X |
At |
term |
X |
|
|
Observed Organs |
Observations |
|||||
* SOPHAGUS * STOMACH * DUODENUM * JEJUNUM * ILEON * CAECUM * COLON * RECTUM * SPLEEN * LIVER |
X X X X X X X X XX |
N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. |
|||||
* THYMUS |
X |
N.t.R. |
|||||
* TRACHEA * LUNGS * HEART |
XXX |
N.t.R. N.t.R. N.t.R. |
|||||
* KIDNEYS * URINARYBLADDER * OVARIES * UTERUS |
X X X X |
N.t.R. N.t.R. N.t.R. N.t.R. |
|||||
* TREATMENT AREA |
- |
- |
|||||
* ADRENALS * PANCREAS |
XX |
N.t.R. N.t.R. |
|||||
PARTICULARS: None |
|||||||
Found dead: GENERAL APPEARANCE |
|
Euthanasia: BEFORE AUTOPSY:Normal |
X |
At |
term |
X |
|
|
Observed Organs |
Observations |
|||||
* ESOPHAGUS * STOMACH * DUODENUM * JEJUNUM * ILEON * CAECUM * COLON * RECTUM * SPLEEN * LIVER |
X X X X X X X X XX |
N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. N.t.R. |
|||||
* THYMUS |
X |
N.t.R. |
|||||
* TRACHEA * LUNGS * HEART |
X X X |
N.t.R. N.t.R. N.t.R. |
|||||
* KIDNEYS * URINARYBLADDER * OVARIES * UTERUS |
X X X X |
N.t.R. N.t.R. N.t.R. N.t.R. |
|||||
* TREATMENT AREA |
- |
- |
|||||
* ADRENALS * PANCREAS |
XX |
N.t.R. N.t.R. |
|||||
PARTICULARS: None |
|||||||
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- EU Criteria
- Conclusions:
- The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.
- Executive summary:
The acute oral toxicity of the test item has been tested in accordance with OECD 423 and EU B.1 tris, under GLP conditions. A limit test was performed, where the test item was administered to a total of 6 female Sprague-Dawley rats (class method) at the dose of 2000 mg/kg body weight by oral gavage. All animals were observed immediately after administration for the onset of any toxic signs and once daily thereafter for 14 days. No mortality occurred during the study and the body weight evolution of the animals remained normal during the study. The decrease of spontaneous activity (6/6), muscle tone (5/6) and righting reflex (5/6) was noted a t30 minutes post dose. The animals recovered normal activity at 24 hours post dose. Macroscopic examination of the animals at the end of the study did not reveal treatment related changes. No other signs of systemic toxicity were noted. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat.
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