Reaction mass of 2,2'-[methylenebis(oxymethylene)]bis[2-ethylpropane-1,3-diol]and propylidynetrimethanol and 2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23rd May 2012 to 9th August 2012.

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:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-diethyl-2,6-bis(hydroxymethyl)heptane-1,3,5,7-tetrol; 2-ethyl-2-(hydroxymethyl)propane-1,3-diol; 2-ethyl-2-{[2-ethyl-3-hydroxy-2-(hydroxymethyl)propoxy]methyl}propane-1,3-diol

EC Number:

904-155-3

Molecular formula:

C12H28O6 C12H26O5 C6H14O3

IUPAC Name:

2,6-diethyl-2,6-bis(hydroxymethyl)heptane-1,3,5,7-tetrol; 2-ethyl-2-(hydroxymethyl)propane-1,3-diol; 2-ethyl-2-{[2-ethyl-3-hydroxy-2-(hydroxymethyl)propoxy]methyl}propane-1,3-diol

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): HB TMP
- Analytical purity: 69%
- Composition of test material, percentage of components: 2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol] (CAS: 23235-61-2, EC No.: 245-509-0), Propylidynetrimethanol (CAS: 77-99-6, EC No.: 201- 074-9) and 2,2'-[methylenebis(oxymethylene)]bis[2-ethylpropane-1,3-diol] (CAS: 93983-16-5, EC No.: 301-304-9).
- Lot/batch No.: 7LTQA002
- Expiration date of the lot/batch: 8th May 2014
- Storage condition of test material: Stored at ambient temperature in the dark when not in use.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Manston Road, Margate, Kent, UK
- Age at study initiation: 8 to 11 weeks old.
- Weight at study initiation: 226.1 to 244.2g.
- Fasting period before study: Animals were fasted overnight prior to dosing.
- Housing: Animals were housed in groups of 3 in appropriately sized solid-bottomed polycarbonate cages with stainless steel mesh tops. Cages were suspended on movable racks and wood shavings were used as bedding.
- Diet (e.g. ad libitum): SDS Rat and Mouse (modified) No. 1 Diet SQC Expanded was provided ad libitum throughout the study.
- Water (e.g. ad libitum): Water from public supply was provided ad libitum.
- Acclimation period: At least 9 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The environmental daily average temperature was approximately 20°C.
- Humidity (%): The range of daily average relative humidity was approximately 45% to 57%.
- Air changes (per hr): Minimum of 10 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Milli-Q water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg.

DOSAGE PREPARATION (if unusual):
Formulations were prepared on each day of dosing. The test item was placed in a sealed bag and immersed in a water bath that was set to a maximum temperature of 80°C until it was visibly homogeneous. The required amount of HB TMP was weighed into a pre-labelled container and formulations were made up to the final volume by adding the requisite amount of Milli-Q water. Formulations were stirred using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg was selected as a suitable starting dose level for administration to Group 1 animals, as recommended in OECD Guideline No. 423. There were no adverse signs recorded in any animal. In order to minimise the number of animals used, the repeat administration of the 300 mg/kg dose level to Group 2 animals was not performed and instead selected a dose level of 2000 mg/kg from the 4 fixed dose levels presented in the OECD Guideline. There were no signs of systemic toxicity in these animals either and so a third group of rats was treated at the same dose level to complete the study.

Doses:

300 and 2000 mg/kg.

No. of animals per sex per dose:

3 females per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Prior to dosing on day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes. The necropsy consisted of an examination of the cranial, thoracic and abdominal organs and tissues in situ.
- Other examinations performed: clinical signs, body weight, other: mortality and moribundity.

Statistics:

No formal statistic analysis was conducted.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the observation period.

Clinical signs:

other: Clinical signs were restricted to 2 animals that were treated with HB TMP at 2000 mg/kg. Animal 6 displayed a red nasal discharge predose and immediately and approximately 30 min post dose on Day 1. Staining around the muzzle of Animal 4 and Animal 6 wa

Gross pathology:

Necropsy on Day 15 revealed no macroscopic abnormalities in any animal.

Other findings:

No additional information applicable.

Any other information on results incl. tables

No additional 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 LD50 of HB TMP in Sprague-Dawley was not classified.

Executive summary:

The acute oral toxicity of HB TMP was investigated in an study conducted using the Acute Toxic Class method, according to OECd Test Guideline 423. In the study, a single oral (gavage) dose of the test substance at 300, 2000 or 2000 mg/kg bw was administered to three respectie groups of female Sprague-Dawley rats. Animals were observed for 14 days after the day of dosing. All animals survived treatment. No treatment-related adverse clinical skigns and no macroscopic abnormalities were recorded in any animal. Bodyweights were considered to be acceptable for rats of this age and strain. Under the condistions of the study, the median lethal dose of HB TMP in Sprague-Dawley rats was > limit dose of 2000 mg/kg and the substance was therefore considered to be unclassofied according to the Globally Harmonised Classification System.