Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and lauric acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 12, 2012 to June 29, 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)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

RD04/201

IUPAC Name:

RD04/201

Details on test material:

- Name of test material (as cited in study report): RD04/201
- Substance type: Clear colourless viscous liquid
- Physical state: liquid
- Purity: UVCB, 100%
- Lot/batch No.: LABO 22935S01Z99
- Expiration date of the lot/batch: 26 April 2014
- Storage condition of test material: At room temperature protected from light
- Hygroscopic: No
- Volatile: No
- Reactivity: Reactive to light
- Test substance handling: Use amber-coloured glassware or wrap container in aluminium foil
- Specific Gravity / Density: 1.14
- Stability at higher temperatures: Yes, maximum temperature: 60°C
- Maximum duration: 24 hours
- Stability in vehicle:
• Propylene glycol Not indicated
- Solubility in vehicle:
• Propylene glycol Not indicated

Test animals

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (first group: 172 - 179 grams; second group: 177 - 196 grams).
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From 12 to 29 June 2012

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE Propylene glycol (Merck, Darmstadt, Germany) (specific gravity 1.036).
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. The test substance and formulation were protected from light by using amber-coloured glassware. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance formulations were heated in a water bath with a maximum temperature of 30.0ºC for a maximum of 51 minutes.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

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.

Clinical signs:

other: Hunched posture and/or piloerection were noted in all animals on Day 1. In addition, one animal showed uncoordinated movements on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Conclusions:

An acute oral LD50 >2000 mg/kg bw was determined for the test substance.

Executive summary:

The acute oral toxicity test was conducted according to OECD  guideline 423, EU method B.1, EPA OPPTS 870.1100, JMAFF guidelines, and GLP principles. Female wistar rats were dosed 2000 mg/kg bw of test substance by gavage. No mortality or abnormal findings were reported. An acute oral LD50 >2000 mg/kg bw was determined for the test substance (Wil, 2012).