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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 20, 2012 to July 04, 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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal 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:

standard acute method

Limit test:

yes

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
- pH: Not indicated
- 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:

male/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. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males: 286 - 300 grams; females: 189 - 208 grams).
- Housing: Individual housing 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: 20 June to 14 July 2012

Administration / exposure

Type of coverage:

occlusive

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

VEHICLE
- The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg body weight

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle and the test substance. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance formulation was heated in a water bath with a maximum temperature of 30.4ºC for a maximum of 55 minutes.

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:

None.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: Hunched posture, chromodacryorrhoea and/or ptosis were noted in two males and four females on Day 1. Scabs and/or scales were seen in the treated skin-area of some animals during the observation period.

Gross pathology:

One male showed reddish discoloration of the thymus at macroscopic examination. No other abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Conclusions:

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

Executive summary:

The acute dermal toxicity test was conducted according to OECD guideline 402, EU method B.3, EPA OPPTS 870.1200, JMAFF guidelines, and GLP principles. Male and female wistar rats were exposed in occlusive condition to 2000 mg/kg bw of test substance for 24 h. No mortality was reported. An acute dermal LD50 of >2000 mg/kg bw was determined for the test substance (Wil, 2012).