Reaction mass of 2-(3-ethylphenyl)oxirane and 2,2’-(1,3-phenylene)dioxirane and 2,2'-(1,4-phenylene)dioxirane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 28 October 2009 and 12 November 2009.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: 15/09/2009 Date of Signature on GLP certificate: 26/11/2009

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of bis(epoxyethyl) benzene and (ethylphenyl) oxirane

IUPAC Name:

Reaction mass of bis(epoxyethyl) benzene and (ethylphenyl) oxirane

Constituent 2

Reference substance name:

Reaction mass of 2-(3-ethylphenyl)oxirane and 2,2’-(1,3-phenylene)dioxirane and 2,2'-(1,4-phenylene)dioxirane

EC Number:

935-853-6

IUPAC Name:

Reaction mass of 2-(3-ethylphenyl)oxirane and 2,2’-(1,3-phenylene)dioxirane and 2,2'-(1,4-phenylene)dioxirane

Details on test material:

- Name of test material (as cited in study report): Reaction mass of bis(epoxyethyl) benzene and (ethylphenyl) oxirane
- Substance type: Organic, Multiconstituent
- Physical state: clear extremely pale yellow liquid
- Analytical purity: 80 - 95%
- Lot/batch No.: 200901317-17
- Stability under test conditions : Stable
- Storage condition of test material : approximately 4°C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test Animals:
Animals: Rat, HsdRccHan: WIST

Breeder: Harlan Laboratories UK Limited, Bicester, Oxon, UK.

Number of Animals per Group: 5 males and 5 females

Total number of Animals: 5 males and 5 females

Age at study initiation: eight to twelve weeks of age

Weight at study initiation: The animals weighed at least 200g, The weight variation did not exceed ± 20% of the mean weight for each sex.

Identification: After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

Acclimatization: At least 5 days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions:

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Accommodation:
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.

Diet:
Free access food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

Water:
Free access to mains drinking water was allowed throughout the study. The drinking
water was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair.

Using available information on the toxicity of the test material, a single group of animals was treated as follows:

Dose Level Specific Gravity Dose Volume Number of Rats
(mg/kg) (ml/kg) Male Female
2000 1.120 1.79 5 5

Duration of exposure:

24 hours

Doses:

2000 mg /kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened
with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourte The animals were returned to group housing for the remainder of the study period.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and
scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the
Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:

Statistics:

No statistical analysis was performed.

Results and discussion

Preliminary study:

Not reported

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits not reported.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Signs of systemic toxicity noted were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration and pilo-erection. Animals appeared normal eight to eleven days after dosing. Signs of dermal irritation noted were well-defined er

Gross pathology:

Small areas of subcutaneous haemorrhage were noted at the site of test material application of all animals. No other abnormalities were noted at necropsy.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.

Executive summary:

Introduction. The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

-  Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

Method. A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations.  Signs of systemic toxicity noted were hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration and pilo-erection. Animals appeared normal eight to eleven days after dosing.

Dermal Irritation.  Signs of dermal irritation noted were well-defined erythema, slight to moderate oedema (on occasions extending ventrally below test site), blanching of the skin, hardened dark brown/black coloured scab, small superficial scattered scabs, scab cracking and scab lifting to reveal glossy skin or bleeding. Adverse reactions prevented accurate evaluation of erythema and oedema from Day 4 until the end of the study on Day 14. The reactions noted at Day 14 were considered to be indicative of dermal corrosion.

Bodyweight.  Nine animals showed bodyweight loss or no gain in bodyweight during the first week but expected gain in bodyweight during the second week. The remaining animal showed expected gains in bodyweight over the study period.

Necropsy.  Small areas of subcutaneous haemorrhage were noted at the site of test material application of all animals. No other abnormalities were noted at necropsy.

Conclusion.  The acute dermal median lethal dose (LD₅₀) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.