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

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

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

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

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).

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

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

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

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.

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

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 LD50 >2000 mg/kg bw was determined for the test substance (Wil, 2012).

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 were reported. The acute dermal toxicity LD50 of >2000 mg/kg bw was determined for the test substance (Wil, 2012).

 

Justification for classification or non-classification

An LD50 (oral) >2000 mg/kg bw and LD50 (dermal) >2000 mg/kg bw were determined for the test substance. Based on these results, the test substance does not warrant classification as per the EU CLP Regulation (EC) No 1272/2008.