2-ethylhexyl 2-([1,1'-biphenyl]-4-ylcarbonyl)benzoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 August 2020 to 24 November 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017

Deviations:

no

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-ethylhexyl 2-([1,1'-biphenyl]-4-ylcarbonyl)benzoate

EC Number:

278-051-5

EC Name:

2-ethylhexyl 2-([1,1'-biphenyl]-4-ylcarbonyl)benzoate

Cas Number:

75005-95-7

Molecular formula:

C28H30O3

IUPAC Name:

2-ethylhexyl 2-{[1,1'-biphenyl]-4-carbonyl}benzoate

Test material form:

liquid

Details on test material:

Purity/Composition: 96.27%
Storage Conditions: At room temperature
Test Facility test item number: 210244/A
Test item handling: No specific handling conditions required
CAS number: 75005-95-7
EC Number: 278-051-5
Substance Name: 2-ethylhexyl 2-([1,1'-biphenyl]-4-ylcarbonyl)benzoate

Specific details on test material used for the study:

Physical Description: Colourless to pale yellow liquid (determined by Charles River Den Bosch)
Purity/Composition: 96.27%
Storage Conditions: At room temperature
Purity/Composition correction factor: No correction factor required
Test item handling: No specific handling conditions required

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Rationale for use of males (if applicable)
- Age at study initiation: approximately 12 weeks old
- Weight at study initiation: 187 to 207 g
- Fasting period before study: not reported
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized wooden fibers as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Historical data: not reported
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.
- Microbiological status when known: Before the initiation of dosing, a health inspection was performed and any assigned animal considered unsuitable for use in the study were replaced by alternate animals obtained from the same shipment and maintained under the same environmental conditions.
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to the study at the discretion of the coordinating biotechnician.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 44 to 70%
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation)
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 27 August 2020 To: 30 September 2020

Administration / exposure

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10%
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution): 2000 mg/kg
- Constant volume or concentration used: yes
- For solids, paste formed: not reported

VEHICLE
- Amount(s) applied (volume or weight with unit): not reported
- Concentration (if solution): not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

2

Control animals:

other: Adjacent areas of untreated skin of each animal served as controls.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes
- Other examinations performed: not reported

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: No relevant clinical signs were noted in any of the animals.

Gross pathology:

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

Any other information on results incl. tables

Skin flaking of the left canthus was observed in one animal between Days 6 and 10 but was considered not test item related at the location observed.

No irritation was noted for any of the animals at any time point.

The incidence of very slight body weight loss between Days 8 and 15 in one individual animal was considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of C991 in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Based on these results, C991 does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

Initially, the test item was administered to a single female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours in a range finder study. Based on the results, the main study was performed by dosing two additional females at 2000 mg/kg. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).
No mortality occurred.
No relevant clinical signs were noted in any of the animals. No irritation was noted for any of the animals at any time point.
The mean body weight gain shown by the animals during the observation period was within the range expected for rats used in this type of study.
No abnormalities were found at macroscopic post mortem examination of the animals.
The dermal LD50 value of the test item in Wistar Han rats was established to exceed 2000 mg/kg body weight.
Based on these results, the test item does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).