Reaction product of 2-hydroxybenzoic acid, styrene and oxozinc

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-02-08 to 2011-02-23

Reliability:

1 (reliable without restriction)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

hexazinc(2+) bis(2-hydroxy-3,5-bis[(1R)-1-phenylethyl]benzoate) bis(2-hydroxy-3,5-bis[(1S)-1-phenylethyl]benzoate) 2-hydroxy-3-(1-phenylethyl)-5-(1-{4-[(1R)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-3-(1-phenylethyl)-5-(1-{4-[(1S)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-3-[(1R)-1-phenylethyl]benzoate 2-hydroxy-3-[(1S)-1-phenylethyl]benzoate 2-hydroxy-5-(1-phenylethyl)-3-(1-{4-[(1R)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-5-(1-phenylethyl)-3-(1-{4-[(1S)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-5-[(1R)-1-phenylethyl]benzoate 2-hydroxy-5-[(1S)-1-phenylethyl]benzoate

EC Number:

700-321-2

Molecular formula:

C30H26O6Zn, C46H42O6Zn, C62H58O6Zn

IUPAC Name:

hexazinc(2+) bis(2-hydroxy-3,5-bis[(1R)-1-phenylethyl]benzoate) bis(2-hydroxy-3,5-bis[(1S)-1-phenylethyl]benzoate) 2-hydroxy-3-(1-phenylethyl)-5-(1-{4-[(1R)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-3-(1-phenylethyl)-5-(1-{4-[(1S)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-3-[(1R)-1-phenylethyl]benzoate 2-hydroxy-3-[(1S)-1-phenylethyl]benzoate 2-hydroxy-5-(1-phenylethyl)-3-(1-{4-[(1R)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-5-(1-phenylethyl)-3-(1-{4-[(1S)-1-phenylethyl]phenyl}ethyl)benzoate 2-hydroxy-5-[(1R)-1-phenylethyl]benzoate 2-hydroxy-5-[(1S)-1-phenylethyl]benzoate

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Laboratoire Elevage Janvier, B.P. 4105, Route des Chênes Secs, 53940 Le Genest-St-Isle CEDEX FRANCE
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 231 – 238 g
- Fasting period before study: overnight fast prior to dosing
- Housing: in groups of 3 animals, in polycarbonate cages
- Diet: laboratory rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 + -3 °C
- Humidity: 24-64 % *)
- Photoperiod: 12 hrs dark / 12 hrs light
*) The relative humidity (24-64%) was slightly out of the target range (30-70%) during the study. This deviation has no impact on the outcome of the study and interpretation of the results.

IN-LIFE DATES: From: 2011-01-13 to 2011-02-23

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle/Amount administered: 200 mg/mL in Dimethyl Sulfoxide (DMSO); dosing volume of 10 mL/kg bw.
- Justification for choice of vehicle: selected as a suitable vehicle for the study purposes based on test item properties and trial formulations
- Batch No. /Lot No. (DMSO): BCBC5888V

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose:
The initial dose level was selected as the one which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Initially, three female animals were treated with 2000 mg/kg bw of Reaction Product of 2-Hydroxybenzoic Acid, Styrene and Oxozinc. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. One animal died in this second dose group, further testing was not required according to the test guidelines (OECD 423, Commission Regulation (EC) No 440/2008, B.1.tris).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females/groups

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
All animals were weighed on allocation to the study (Day -1), immediately prior to
dosing (Day 0), on Day 7 and prior to necropsy.
Further examinations performed:
Clinical signs: Animals were observed for clinical signs immediately upon dosing, and approximately at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily thereafter for a total of 14 days.

Statistics:

NA

Results and discussion

Preliminary study:

NA

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Reaction Product of 2-hydroxybenzoic acid, styrene and oxozinc caused mortality in one animal at a dose level of 2000 mg/kg bw.

Clinical signs:

other: Treatment with Reaction Product of 2-hydroxybenzoic acid, styrene and oxozinc caused decreased activity (5/6), in coordination (1/6) and general body tone (1/6) during the 14 days observation period

Gross pathology:

Amber coloured mucoid material found in the digestive content of the small intestines was considered to be test item-related in the found dead animal. No macroscopic observations were noted in remaining animals at a dose level of 2000 mg/kg bw.

Other findings:

No other findings.

Any other information on results incl. tables

No other information

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Reaction Product of 2-hydroxybenzoic acid, styrene and oxozinc was found to be above 2000 mg/kg bw in female RjHan:WI rats.

Executive summary:

In an acute oral toxicity study according to OECD TG 423 (2001) and under GLP, 2 groups/3 females of fasted, young adult Sprague-Dawley rats were given a single oral dose of the test substance in Dimethyl Sulfoiyde (DMSO) at 2000 mg/kg bw and consecutively observed for 14 days.

Initially, 3 females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. One animal died in the confirmatory group, therefore no further testing was required according to OECD 423 (2001) and Commission Regulation (EC) No 440/2008. No mortality occurred and no signs of toxicity were observed during the 14 day observation period. All animals showed slight clinical signs of piloerection and production of soft faeces 4 hours after dosing. Recovery had occurred within 24 hours and no other signs of reaction to treatment were apparent during the 14 day observation period. The bodyweight gain was not impaired. Thus, the oral LD50 was determined to be >2000 mg/kg bw.