[1,1'-Biphenyl]-2-carboxylic acid, 4'-(bromomethyl)-, methyl ester

Endpoint summary

Description of key information

Skin irritation: Test method OECD 430 and EU B.40. GLP study. The test item did not lead to skin corrosion/severe irritation.
Eye irritation: Test method OECD 438 and EU B.48. GLP study. The test item did not cause eye damage. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

Remarks:

in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 November 2013 - 11 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test method according to OECD Guideline 430. GLP study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

SOURCE OF THE BIOLOGICAL MATERIAL:
TEST ANIMALS:
- Source: Centre for Experimental Medicine at the Medical University in Katowice
- Age at study initiation: At the beginning of the experiment, the animals were 25 days old. The skin discs used in the experiment were obtained from two 29-day-old female rats.
- Housing: Plastic cage covered with a wire bar lid. Dimensions: 58 x 37 x 21 cm. Bedding: UV-sterilized wood shavings.
- Diet (e.g. ad libitum): ad libitum, "Murigran” standard granulated laboratory fodder
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20ºC
- Humidity (%): 49-52%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Type of coverage:

other: Not applicable: in-vitro test

Preparation of test site:

other: Not applicable: in-vitro test

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

VEHICLE
- Amount(s) applied (volume or weight with unit): 150 µl of distilled water

Duration of treatment / exposure:

24 hours

Number of animals:

2

Irritant / corrosive response data:

On the grounds of the study, it may be stated that the test item belongs to a group of substances which do not lead to skin corrosion/severe irritation. The mean TER values for the test item were higher than 5 kΩ and there were not any visible changes on the skin discs.

Results of the control transcutaneous electrical resistance test (TER):

Animal number	Skin disc number	TER value (kΩ)
1	1	15.23
	2	14.39
2	1	17.35
	2	15.98

The skin discs gave the resistance values greater than 10 kΩ; therefore, the remainder of the skin discs of the animals could have been used in the experiment.

Results of the transcutaneous electrical resistance test (TER):

Animal number	Tested substance	Skin disc number	TER value (kΩ)	Mean TER value ± SD (kΩ)
1	Positive control – 36% HCl	1	0.93	0.92 ± 0.03
		2	0.89
		3	0.94
	Negative control – distilled water	1	19.22	18.76 ± 0.44
		2	18.71
		3	18.35
	Test item	1	20.41 | 20.43*	20.82 ± 0.42
		2	21.15 | 21.13*
		3	20.49 | 20.52*
2	Positive control – 36% HCl	1	0.95	0.93 ± 0.03
		2	0.93
		3	0.90
	Negative control – distilled water	1	20.32	19.02± 1.19
		2	18.75
		3	17.98
	Test item	1	13.48	14.43 ± 1.16
		2	14.09
		3	15.72

The concurrent mean values for the positive and negative controls were within the acceptable ranges for the method:

Positive control: 0.89 -0.95 kΩ

Negative control: 17.98 -20.32 kΩ

The mean TER results for the skin discs treated with the test item were equal to 20.82 kΩ (animal no. 1) and 14.43 kΩ (animal no. 2).

Gross changes on the surface of the treated skin discs:

Animal number	Tested substance	Skin disc number	Gross changes
1	Positive control – 36% HCl	1	perforation
		2	perforation
		3	perforation
	Negative control – distilled water	1	no changes
		2	no changes
		3	no changes
	Test item	1	no changes
		2	no changes
		3	no changes
2	Positive control – 36% HCl	1	perforation
		2	perforation
		3	perforation
	Negative control – distilled water	1	no changes
		2	no changes
		3	no changes
	Test item	1	no changes
		2	no changes
		3	no changes

The gross examination showed that the positive control skin discs exhibited skin perforation, whereas the negative control skin discs and the ones treated with the test item did not reveal any changes.

Interpretation of results:

other: non-corrosive

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The substance do not lead to skin corrosion/severe irritation. The mean TER values for the test item were higher than 5 kΩ and there were not any visible changes on the skin discs.

Executive summary:

The in vitro skin corrosion: transcutaneous electrical resistance test (TER) was performed according to OECD Guideline 430 Guideline and EU Method B.40. (GLP study). Skin discs used in the experiment were obtained from two 29-day-old rats. The test item (ground to a powder) was uniformly applied to the epidermal surface of the skin disc placed inside a tube. Positive (36% hydrochloric acid) and negative (distilled water) controls were conducted concurrently. Three skin discs obtained from each animal were used for the test item and three for each control item. The test item and the control items were evenly applied to the discs for 24 hours and kept at 21-22°C. Then, they were removed by washing with a jet of tap water and the surface tension of the skin was reduced by adding 70% ethanol. After removing the ethanol the tissue was hydrated by the addition of 3 mL of a solution of MgSO4 (154 mM). A LCR 6401 low-voltage, alternating current databridge was used to measure the electrical resistance of the skin in kΩ by placing the databridge electrodes on either side of the skin disc. The skin discs were subjected to a gross examination. The mean TER results were equal to 20.82 kΩ (animal no. 1) and 14.43 kΩ (animal no. 2). The concurrent positive and negative control values fell within the acceptable ranges for the method. Gross examinations of the skin discs did not reveal any pathological changes. On the grounds of the study, it may be stated that the test item do not lead to skin corrosion/severe irritation. The mean TER values for the test item were higher than 5 kΩ and there were not any visible changes on the skin discs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation/corrosion: Key study: The in vitro skin corrosion: transcutaneous electrical resistance test (TER) was performed according to OECD Guideline 430 Guideline and EU Method B.40. (GLP study). The mean TER results for the skin discs (rat) treated with the test item for 24 hours were equal to 20.82 kΩ (animal no. 1) and 14.43 kΩ (animal no. 2). The concurrent positive and negative control values fell within the acceptable ranges for the method. Gross examinations of the skin discs did not reveal any pathological changes. On the grounds of the study, the test item do not lead to skin corrosion/severe irritation.

Eye irritation: Key study: The isolated chicken eye test (in vitro) was performed according to OECD Guideline 438 and EU Method B.48 (GLP study). On the grounds of the study results and the overall in vitro Irritancy Classification, it may be stated that the test item, did not cause eye damage. According to UN GHS classification criteria, no Category, since the ICE Class combination of the 3 endpoints was 3xl.

Justification for selection of skin irritation / corrosion endpoint:
Only one study is available.

Justification for selection of eye irritation endpoint:
Only one study is available.

Justification for classification or non-classification

Based on the available information, the substanc has no Category for eye irritation, since ICE Class combination of the 3 endpoints was 3xl.