Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with diethylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 June 2012 - 18 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

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:

Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with diethylamine

EC Number:

500-425-6

EC Name:

Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with diethylamine

Cas Number:

159034-91-0

Molecular formula:

Not available for this UVCB

IUPAC Name:

Reaction product of poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-[(1-oxo-2-propenyl)oxy]-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1) and N-ethylethanamine

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 222 g (range: 212 g to 238 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: the animals were acclimated to the study conditions for a period of 5 or 8 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 26 June 2012 to 13 July 2012.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle:
The vehicle used in the study was selected from the results of solubility assays performed by CIToxLAB France prior to the preliminary assay.
The solubility assay first started with drinking water treated by reverse osmosis and 0.5% methylcellulose aqueous solution and was not satisfactory. However, a yellow suspension was obtained at 200 mg/mL with corn oil.
- Maximum dose-volume applied: 20 mL/kg.

DOSAGE PREPARATION (if unusual):
The test item was administered as a homogeneous suspension in the vehicle. The test item was mixed under magnetic agitation with the required quantity of vehicle.
Dose formulations preparations were prepared by the CiToxLAB France Pharmacy extemporaneously on the day of each administration.
The dose formulations were stored at room temperature and delivered to the study room in brown flasks.

CLASS METHOD (if applicable):
Rationale for dose-level selection
The starting dose-level was selected in agreement with the Sponsor, based on the following rationale:
- based on available test item toxicity data, no morbidity or mortality was expected to occur at the dose level of 2000 mg/kg. This was therefore chosen as the starting dose-level.

Doses:

2000 mg/kg.

No. of animals per sex per dose:

3 females per treatment step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Statistics:

no

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: Piloerection was observed in 4/6 females within 4 hours after treatment. No clinical signs persisted from day 2.

Gross pathology:

The only macroscopic finding noted (red discoloration in the thymus in a single female) at the end of the observation period is commonly recorded in the Sprague-Dawley rat and was considered to be incidental and not to be related to the test item administration.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD0 of the test item was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats,according to OECD No. 423 (2001) and EU Method B.1tris (2008) guidelines.

This study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item was administered once by oral route (gavage) to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil.

Based on available test item toxicity data, the starting dose-level of 2000 mg/kg was chosen. After the first assay, as no toxicity was observed, the results were confirmed in three other females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study reportas no microscopic examination was performed.

Results

No unscheduled deaths occurred during the study.

Piloerection was observed in 4/6 females within 4 hours after treatment. No clinical signs persisted from day 2.

When compared to CiToxLAB France historical control data, a lower body weight gain was noted in 3/6 females between day 8 and day 15.

The test item administration did not induce any macroscopic changes.

Conclusion

The oral LD₅₀of the test item was higher than 2000 mg/kg in rats.

 Therefore, the test item is not classified as toxic or harmful by oral route according to the criteria of CLP Regulation.