oligomeric reaction product of 2-hydroxybenzaldehyde with 1-chloro-2,3-epoxypropane and phenol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 June 2016- 21 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

These deviations are considered to have no impact on the outcome of the study or on the interpretation of the results.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-({2-[bis({2-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-({2-[bis({4-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-{[2-({2-[(oxiran-2-yl)methoxy]phenyl}({4-[(oxiran-2-yl)methoxy]phenyl})methyl)phenoxy]methyl}oxirane

EC Number:

942-639-6

IUPAC Name:

2-({2-[bis({2-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-({2-[bis({4-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-{[2-({2-[(oxiran-2-yl)methoxy]phenyl}({4-[(oxiran-2-yl)methoxy]phenyl})methyl)phenoxy]methyl}oxirane

Test material form:

solid

Details on test material:

Name: EPICLON EXA-7250
Batch/Lot number: B006
Appearance: Brown solid (in smaller amount colour is yellow)
Purity: >99%
Manufacture date: 02 October 2014
Expiry date: 02 March 2017
Storage condition: Room temperature 15-25°C, below 70 RH%
Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses, face
mask) for unknown materials were applied to assure personnel
health and safety.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:B006
- Expiration date of the lot/batch:02 March 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:Controlled Room Temperature (15-25oC, below 70 % RH)


FORM AS APPLIED IN THE TEST: yes

Test animals

Species:

rat

Strain:

other: Crl:WI rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats Males: 7 weeks; Females: 8-9 weeks
- Weight at study initiation: Males: 215-234 g; Females: 214-237 g
- Fasting period before study: 24 hours
- Housing:Individual caging, Type II. polypropylene/polycarbonate cages. Lignocel 3/4 S, produced by J. Rettenmaier & Söhne GmbH+Co. KG Holzmühle 1, D-73494 Rosenberg, Germany, as certified bedding for laboratory animals was available to rats during the study.
- Diet and water (e.g. ad libitum): Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D- 59494, Soest, Germany (Batch no.: 278 5652, Expiry date: November 2016), ad libitum, and tap water from municipal supply, as for human consumption was provided from 500 ml bottles, ad libitum. The food was considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 – 24.9 °C
- Humidity (%): 41 – 69 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From:02 June 2016 To: 21 June 2016

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
The back of the animals were shorn (approximately 10% area of the total body surface) approximately 24 hours prior to the treatment. Only the animals without injury or irritation on the skin were used in the test. On the test day (Day 0), the test item was applied as a single dose of 2000 mg/kg
bw after the moistening with sufficient water, applied uniformly over the skin by use of a gauze pad (ca. 5 cm x 5 cm), and remained on the skin throughout an approximately 24-hour exposure period. Sterile gauze pads were placed on the skin of rats at the site of application. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for approximately 24 hours. At the end of the exposure period, residual test item was removed, using body temperature water.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, residual test item was removed, using body temperature water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):Single dose of 2000 mg/kg bw

Duration of exposure:

24 Hours

Doses:

Single dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 Females per dose
5 Males per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A clinical examination was performed on the day of treatment, at 2 and 5 hours after the application of the test item, and once each day for 14 days thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.

Macroscopic examination was performed on all animals. All animals were anaesthetised with pentobarbital sodium (details in 3. 3) and exsanguinated. After
examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.

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 after approximately 24-hour dermal exposure to EPICLON EXA-7250 in Crl:WI rats.

Clinical signs:

other: Each rat was symptom-free during the entire study. No local dermal signs were recorded after treatment with the test item during the 14 days observation period.

Gross pathology:

No external or internal macroscopic findings were observed at a dose level of 2000 mg/kg bw at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The median lethal dose (LD50) of EPICLON EXA-7250 after a single dermal administration was found to be greater than 2000 mg/kg bw in male and
female Crl:WI rats. According to the GHS criteria, EPICLON EXA-7250 can be ranked as "Category 5" or "Unclassified" for acute dermal exposure.

Executive summary:

The purpose of the study was to assess the acute dermal toxicity of EPICLON EXA-7250 when administered to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days. The test item was applied dermally to ten (5 males and 5 females) Crl:WI rats as supplied by the Sponsor. A limit test was carried out at 2000 mg/kg body weight (bw) in both

sexes.

Clinical observations were performed on all animals at 2 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Rats were euthanized and subjected to a gross

macroscopic examination at the end of the 2-week observation period (Day 14).

The results of the study were summarized as follows:

Mortality

No mortality occurred after approximately 24-hour dermal exposure to EPICLON EXA-7250 in Crl:WI rats.

Systemic clinical signs

Each rat was symptom-free during the entire study.

Local dermal signs

No local dermal signs were recorded after treatment with the test item during the 14 days observation period.

Body weight and body weight gain

There were no treatment related changes in the body weights. The body weights of the animals were within the range commonly recorded for this strain and age.

Necropsy

No external or internal macroscopic findings were noted at a dose level of 2000 mg/kg bw at necropsy.

Conclusions

The median lethal dose (LD50) of EPICLON EXA-7250 after a single dermal administration was found to be greater than 2000 mg/kg bw in male and female Crl:WI rats.

According to the GHS criteria, EPICLON EXA-7250 can be ranked as "Category 5" or "Unclassified" for acute dermal exposure.