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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to guideline
other: Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA, 1959
not specified
Deviations from guideline not described
Principles of method if other than guideline:
The experimental procedure is in essence similar to, but uses more animals and higher dosages than would be required, if conducted following the most recent guidelines, Annex V to Dir 67/548/EEC Part B.1 bis: "Acute Oral Toxicity - Fixed Dose Procedure" or OECD TG 420 (2001).
GLP compliance:
No description of GLP or similar procedures
Test type:
fixed dose procedure
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxy-3-{4-[2-(4-{2-hydroxy-3-[(2-methylprop-2-enoyl)oxy]propoxy}phenyl)propan-2-yl]phenoxy}propyl 2-methylprop-2-enoate
EC Number:
Cas Number:
Molecular formula:
2-hydroxy-3-{4-[2-(4-{2-hydroxy-3-[(2-methylprop-2-enoyl)oxy]propoxy}phenyl)propan-2-yl]phenoxy}propyl 2-methylprop-2-enoate
Details on test material:
- Name of test material: 2,2-Bis-4(3'-methacryloyloxy-2'-hydroxy)propoxyphenyl propane
- Molecular formula: Not described
- Molecular weight: Not described
- Smiles notation (if other than submission substance): Not described
- InChl (if other than submission substance): Not described
- Structural formula attached as image file (if other than submission substance): see Fig. Not described
- Origin: Produced and made available for test by Röhm GmbH, Chemische Fabrik, Darmstadt, Germany
- Physical state: Viscous, sticky, colourless, clear fluid
- Analytical purity: Not described
- Composition of test material, percentage of components: Not described
- Isomers composition: Not described
- Purity test date: Not described
- Lot/batch No.: Not described
- Expiration date of the lot/batch: Not described
- Stability under test conditions: Not described
- Storage condition of test material: Not described

Test animals

Details on test animals or test system and environmental conditions:
- Source: Zucht Winkelmann, Paderborn, Germany
- Age at study initiation: Not described
- Weight at study initiation: Between 160 and 240 g (individual weights available in data sheets)
- Fasting period before study: Food, but not water, was removed 16 hours prior to study initiation.
- Housing: Single cages.
- Diet: Standard laboratory diet (Ssniff, Intermast) ad libitum
- Water: Ad libitum
- Acclimation period: Not described

- Temperature: 22°C
- Humidity (%): 45 - 55
- Air changes (per hr): Not described
- Photoperiod (hrs dark / hrs light): 12 hrs dark /12 hrs light.

IN-LIFE DATES: From - To: Not described

Administration / exposure

Route of administration:
oral: gavage
arachis oil
Details on oral exposure:
Test substance was diluted to a concentration of 50% in Oleum arachidis.

- Concentration in vehicle: 50% (vol/vol)
- pH Value of test substance in vehicle: 5.5
- Volume of test substance in solution: from 3.2 ml at the lowest dosage to 8.0 ml at the highest dosage.
- Justification for choice of vehicle: Not described
- Lot/batch no.: Not described
Purity: Not described

MAXIMUM DOSE VOLUME APPLIED: Male rats: 8.0 ml; Female rats: 6.8 ml

- Rationale for the selection of the starting dose: Starting dose found at preliminary study

DOSAGE PREPARATION: Dosis range with intervals of log 0.1.
Four groups of animals were given increasing doses of test substance, diluted to 50% in arachis oil. A single dose was given orally. Listed dosages refers to the undiluted test substance (in ml test substance/kg bodyweight). The given volume of diluted test substance is given as a range in paranthesis:
Group 1: 10.0 ml/kg (3.2 - 3.7 ml)
Group 2: 12.6 ml/kg (4.2 - 5.2 ml)
Group 3: 15.9 ml/kg (5.1 - 6.4 ml)
Group 4: 20.0 ml/kg (5.8 - 8.0 ml)
No. of animals per sex per dose:
Group 1: 10.0 ml/kg : 5 males / 5 females
Group 2: 12.6 ml/kg : 5 males / 5 females
Group 3: 15.9 ml/kg : 5 males / 5 females
Group 4: 20.0 ml/kg : 5 males / 5 females
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observationdata are logged for the following time points after ingestion of the test substance: 20 min, 1 h, 3 h, 24 h, 48 h, 6 and 7 days, and 14 days. Weighing of animals was done at the beginning of the test and after 14 days (survivors only).

- Necropsy of survivors performed: no

- Other examinations performed:
Observation of clinical signs of toxicity was noted at the following time points after ingestion: 20 min, 1 h, 3 h, 24 h, 7 days, and 14 days. Parameters were: Level of consciousness, emotional state, behavioural symptoms (from the CNS), coordination and posture, muscle tonus, reflexes, autonomic functions.
Body weight: at beginning and end of test
Organ weights and macroscopic pathology: performed on animals if they died during test period.
Histopathology was not performed.
Not described

Results and discussion

Preliminary study:
Not described in report.
Effect levelsopen allclose all
Key result
Dose descriptor:
approximate LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality within first 24 h
Key result
Dose descriptor:
Effect level:
>= 14.15 mL/kg bw
Based on:
test mat.
95% CL:
> 13.38 - < 14.92
Remarks on result:
other: Mortality occurred between 48 h and 7 d after exposure
Mortality occurred after 24 h, but within 7 days of ingestion. In the groups dosed with 15.9 ml and 20.0 ml test substance the majority of mortal incidences occurred within 48 h of ingestion.

Group Dosage 24 hours 14 days
I 10.0 ml/kg 0/10 0/10
II 12.6 ml/kg 0/10 3/10
III 15.9 ml/kg 0/10 7/10
IV 20.0 ml/kg 0/10 10/10

Clinical signs:
other: With increasing dosage the test substance did cause the following clinical symptoms of toxicity, starting 20 minutes after ingestion and seizing 24 hours after ingestion. Symptoms (increasing level with increasing dosage): lower activity level, mild coor
Gross pathology:
In animals dying during the test period, acute mortality within 48 hours and delayed mortality within 7 days after ingestion, autopsy findings included erythematous gastric and enteric mucosa, whereas pathological examination revealed no observable changes in other organs incl. CNS, lungs, heart, liver, spleen, kidneys, reproductive organs and the lymphatic system.
Other findings:
- Organ weights: no data described
- Histopathology: Not performed
- Potential target organs: Not described
- Other observations: Females showed a higher mortality rate at 15.9 ml/kg BW than males.

Any other information on results incl. tables


Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Migrated information Even the lowest dosage is above the 2000 mg/kg bw limit for classification of substances as toxic Criteria used for interpretation of results: not specified
Based on a fixed dose acute oral toxicity study in rats, the LD50 (14 d) of Small Vinyl Ester was determined: 14.15 ml/kg bw (13.38 -14.92 ml/kg bw). The LD50 (24 h) was not calculated due to lack of mortality within the first 24 h.The study and data are below current standard, and should be used for supporting data only.
Executive summary:

The acute oral toxicity of Small Vinyl Ester in the rat, was tested in a single dose procedure with a 14 day follow up period. The study was conducted following recommendations from "Appraisal of the safety of chemicals in foods, drugs and cosmetics", by the Staff of the Division of Pharmacology, FDA, 1959. Four groups, each including 5 male and 5 female SPF-Wistar rats, were given a single dose of a test solution, containing 50% test substance and 50% arachidis oil, by gavage, and observed for clinical/behavioural signs of toxicity and mortality. Dose range of the undiluted Small Vinyl Ester was 10.0, 12.6, 15.9, and 20 ml/kg bw. Since the test solution was a 50% dilution of the Small Vinyl Ester the actual volume doses given to the rats were 20.0, 25.2, 31.8 , and 40.0 ml/kg bw.

Clinical symptoms, includin lower activity level, mild coordination disturbances, and disturbances in posture, piloerektion, and diarrheoa, started after 20 min and seized after 24 h, when surviving animals returned to normal habitus. Mortality occurred after 48 h up to 7 d after ingestion. The mortality after 14 days (actually 7 days) was 0/10 in group 1, 3/10 in group II, 7/10 in group III, and 10/10 in group IV. Pathological post mortem examination of the dead animals revealed erythematous gastric and enteric mucosa, but no other observable pathology was found.

On this basis a calculated LD50 after 14 days was 14.15 ml/kg bw (13.38 -14.92 ml/kg bw). The LD50 after 24 h was not calculated due to lack of mortality within the first 24 h.

The given volumes of Small Vinyl Ester and test solutions prepared with 50% arachidis oil are 2-4 times higher than the recommended maximum volumes for acute toxicity testing. Thus it cannot be ruled out that the observed mortality, clinical symptoms and pathology is a result of giving very high volumes of oily solution in a single dose. Still the survival of all animals in groups I (doses of 10.0 ml/kg bw) indicates that Small Vinyl Ester is practically nontoxic. The dose in group I was 10.0 ml/kg bw corresponds to a dose of 11.7 g/kg bw (density of test substanc: 1.17 g/ml, results from Liddiard and Koban, 2008), which is above the recommended upper fixed doses for testing in current standards of acute oral toxicity.