Benzoic acid, 2-([1,1'-biphenyl]-4-ylcarbonyl)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 06, 2014 to May 15, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-{[1,1'-biphenyl]-4-carbonyl}benzoic acid

EC Number:

700-862-4

Cas Number:

42797-18-2

Molecular formula:

C20 H14 O3

IUPAC Name:

2-{[1,1'-biphenyl]-4-carbonyl}benzoic acid

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): 2-(4Phenylbenzoyl)benzoic acid
- Physical state: white powder
- Analytical purity: 99.9%
- Lot/batch No.: 5307
- Expiration date of the lot/batch: 01 May 2015
- Storage condition of test material: room temperature in the dark

Specific details on test material used for the study:

Batch No.: 5307; Purity: 99.9%; Appearane: white powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female Wistar (RccHanÔ:WIST) rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization 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. At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-h exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. 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.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

DMSO

Details on dermal exposure:

For the purpose of the study the test substance was weighed according to each animal’s individual body weight and moistened with dimethyl sulphoxide prior to application.
The extent of absorption of the test substance was not determined.

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 substance, a group of five male and five female rats was treated with the test substance at a dose level of 2000 mg/kg. The appropriate amount of the test substance, moistened with dimethyl sulphoxide, was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area). 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 dimethyl sulphoxide followed by distilled water to remove any residual test substance. The animals were returned to group housing for the remainder of the study period.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five male and five female

Control animals:

not required

Details on study design:

The animals were observed for deaths for overt signs of toxicity at 30 min, 1, 2 and 4 h after dosing and subsequently once daily for fourteen days. 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 scale explained in the section for additional information. Any other skin reactions, if present were also recorded. Individual body weights were recorded prior to application of the test substance on Day 0, 7 and 14. At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

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:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Light brown discoloration of the epidermis was noted at the test sites of three males one and two days after dosing. Reduced regrowth of fur was also noted at the test sites of two of these animals during the study. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Applicant's summary and conclusion

Conclusions:

Under the study conditions, the LD50 of the test substance in Wistar rats was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance PBBA to Wistar rats according to OECD Guideline 402 and EU Method B.3, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 h, semi-occluded dermal application of the test substance to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths or signs of systemic toxicity. Light brown discoloration of the epidermis was noted at the test sites of three males one and two days after dosing. There were no signs of dermal irritation recorded at the test sites of the remaining animals. No abnormalities were seen at necropsy. Under the study conditions, the LD50 of the test substance in Wistar rats was determined to be >2000 mg/kg bw (Pooles, 2014).