Registration Dossier

Administrative data

skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 06 2018 to November 03 2018
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
other: TG 404
Version / remarks:
"Acute Dermal Irritation/Corrosion Test" published by the Ministry of Environmental Protection of People's Republic of China 2013
according to guideline
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Seventh revised edition, 2017, United Nations
Principles of method if other than guideline:
In the study plan, animals will be individually raised in suspended, stainless steel cages (W40 cmxL50 cmxH40 cm) on cage. racks (1167 cmxW70 .cmxHl 71 cm) during the study. But in fact they were individually raised in stainless steel cages (W70 cmxL80 cmxH75 cm) without cage racks. Because the cage racks used were larger than the planned ones, this deviation was considered not to affect the quality and integrity of the study.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
(2-fluoro-3-methoxyphenyl)boronic acid
EC Number:
Cas Number:
Molecular formula:
(2-fluoro-3-methoxyphenyl)boronic acid
Test material form:
solid: particulate/powder

Test animals

other: Japanese White(Albino)
Details on test animals or test system and environmental conditions:
Test System
Species: Albino rabbit
Strain: Japanese White
Grade: Conventional Laboratory Animals
Supplier: Qingdao Kangda Biological Technology Limited Company
License No.: SCXK (Lu) 20160002
Qualification No.: 37003900000709
Justification of Test System: Rabbits are the preferred species of choice as historically used for the safety evaluations studies and are specified in the appropriate test guidelines.
Number: 3 animals
Sex: Male
Age: Young adult, 84 days at arrival and 89~90 days at dosing.
Body Weight Range: 2037.4-2355.0 g at receipt and 2117.3-2690.9 g at dosing.
Physical Check-up and Acclimatization: Physical check-up was made to all animals on arrival. Healthy young adult animals were acclimatized to the laboratory conditions and housed individually for 5~6days prior to dosing, during which clinical observations were performed daily and all animals showed no abnormality. All animals were weighed and marked by the special animal markers beginning from No. 1100 to 1102 and number written on cage cards within 24 hours after arrival.

Test Conditions
Animals were housed in Room A115 of the facility. Animals were individually raised in stainless steel cages (W70 cmxL80cmxH75 cm) during the study.

Environmental Controls
Temperature and humidity were controlled automatically and daily recorded. The values in the aninJal room were 17-23°C for temperature, and 40%-70% for humidity. The lighting sequence was 12 hours light, 12 hours dark.

Food and Water
Animals were provided with rabbit maintenance feed supplied by Beijing Keaoxieli Feed Co., Ltd. Analysis reports of diet were the supplier. All the nutrition components and contaminants were within the permitted limits described in the national standard.
Drinking water was purified by the HT-R0l000 purity system. Water analysis was conducted routinely analyzed (annually), and all parameters were within the permitted limits described in the national standard.
Diet and drinking water were considered not to contain any contaminants that could reasonably be expected to affect the result, purpose and integrity of the study.
Diet and drinking water were available to the animals ad libitum during the test.

Animal Welfare
Animal use comply with national animal welfare laws and regulations (instructive notions with respect to caring for laboratory aninJals) (2006, Ministry of Science, P.R.C.).The aninJal care and use activities required for conduct of this study were reviewed and approved by the testing facility Animal Care and Use Committee (IACUC).

The surviving animals were humanely killed by 10% KCl injection application (1.5 mL/kg) after anesthetized by Zoletil (5 mg/kg) at the end of the study. Their corpse treatments were entrusted to specialized agencies.

Test system

Type of coverage:
Preparation of test site:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g/ test site
Duration of treatment / exposure:
4 hours
Observation period:
24 hours between initial and confirmatory tests.
Number of animals:
3 males
Details on study design:
Observation, Measurement and Examination Clinical Observations
All animals were observed for clinical signs once daily throughout the study.

Skin Reactions Examination
The skin sites after patch removal were examined and recorded for dermal irritation (erythema/eschar, oedema and all local toxic effects of skin) and corrosion (ulcers, bleeding, bloody scabs, etc., by the end of observation).
The skin sites of each animal were examined and recorded for signs of skin reaction immediately, at approximately 1, 24, 48 and 72 hours after patch removal.

Grading of Skin Reactions
Dermal reactions for erythema/eschar or oedema of test sites of each animal were scored and recorded at approximately 1, 24, 48 and 72 hours after patch removal according to the grades in Table2 below.

Body Weights
Individual animal body weight was recorded within 24 hours after arrival, on the day of dosing and on the completion day of the final observations of dermal irritant symptoms.

Histopathological Examination
Histopathological examination was not conducted because there were no equivocal responses.

Evaluation of Data
Summary data in tables covered animal ID, gender, dosage, clinical observations, skin reactions examination, grading of skin reactions and body weights.
Mean scores for erythema/eschar and oedema at 24, 48 and 72 hours after patch removal of the test item for each animal were calculated to assess the degree of dermal irritation/corrosion of the test item in conjunction with the nature and severity of lesions, and their reversibility or lack of reversibility.
The test item was classified according to GHS criteria for the Acute Dermal Irritation/Corrosion.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Time point:
24/48/72 h
Max. score:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Time point:
24/48/72 h
Max. score:
fully reversible
Remarks on result:
no indication of irritation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Based on above results, FMPBA was considered to have no irritations to skins of rabbits, and was classified as "unclassified" according to GHS's classification criteria for the skin irritation.