5-bromo-1,3-dichloro-2-fluorobenzene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Remarks:

The study was conducted to meet the national regulatory requirements in a non-EEA country.

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-bromo-1,3-dichloro-2-fluorobenzene

EC Number:

640-454-2

Cas Number:

17318-08-0

Molecular formula:

C6H2 BrCl2F

IUPAC Name:

5-bromo-1,3-dichloro-2-fluorobenzene

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAGE® Labs
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult (10-12 weeks)
- Weight at study initiation: males 334-376 grams and females 210-239 grams
- Fasting period before study: no
- Housing: Animals were group housed, except on the day of application, at which time they were singly housed until the animals were deemed acceptable, based on observations, to return to group housing.
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Rodent Diet #2016 ad libitum
- Water (e.g. ad libitum): Filtered tap water ad libitum
- Acclimation period: 21 or 29 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 52-77
- Air changes (per hr): 12 or 13
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: Start: June 14, 2018; End: July 11, 2018

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Initial testing was conducted on one male and one female rat to determine extreme clinical signs or severe irritation potential of the test substance. Due to the absence of clinical signs or severe local signs of irritation, an additional four males and four females were tested. Five thousand milligrams of the test substance per kilogram of body weight was applied evenly over a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface) and covered with a 2-inch x 3-inch, 4-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered Day 0 of the study.
After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water and a paper towel to remove any residual test substance.

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw (Individual doses were calculated based on the initial body weights, taking into account the density of the test substance)

No. of animals per sex per dose:

Five (initial test was done with one animal per sex)

Control animals:

no

Details on study design:

The animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.
Individual body weights of the animals were recorded prior to test substance application (initial) and again on day 7 and day 14 (terminal).
All surviving rats were killed by CO2 inhalation at the end of the 14-day observation period.
Gross necropsies were performed on all animals killed at the end of the study. Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

Statistical analysis was limited to the calculation of the mean density value for dosing. Since no deaths occurred at the limit dose, the LD50 was determined without the need of statistical analysis.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: All animals survived test substance administration during the study. Other than the dermal irritation noted at the dose site of all animals between Days 1 and 8, there were no other adverse clinical findings recorded for any animal over the course of the

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the single dose acute dermal median lethal dose (LD50) of CA5528 is greater than 5000 mg/kg of body weight in male and female rats.

Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for CA5528 to produce toxicity from a single topical application.  Initially, 5000 mg/kg of the test substance was applied to the skin of one healthy male rat and one healthy female rat for 24 hours. Due to the absence of clinical signs or severe local signs of irritation, an additional four males and four females were tested.  The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application (initial), on Day 7, and on Day 14 (terminal). Necropsies were performed on all animals.

All animals survived test substance administration and gained body weight during the study.  Other than the dermal irritation noted at the dose site of all animals between Days 1 and 8, there were no other adverse clinical findings recorded for any animal over the course of the study.  No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.