Difluoroacetic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Subacute Oral Exposure to Dibromoacetic Acid Induced Immunotoxicity and Apoptosis in the Spleen and Thymus of the mice

Author:

Shuying Gao, Yan Wang, Ping Zhang, Yucui Dong, and Baixiang Li

Year:

2008

Bibliographic source:

TOXICOLOGICAL SCIENCES 105(2), 331–341 (2008)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The subacute toxicity of dichloroacetic acid on BALB/c mice to determine the toxic effects on the target organs for toxicity.Control: 5 males and 5 females

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibromoacetic acid

EC Number:

211-165-5

EC Name:

Dibromoacetic acid

Cas Number:

631-64-1

IUPAC Name:

dibromoacetic acid

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report): DIBROMOACETIC ACID
- Molecular formula (if other than submission substance): C2H2Br2O2
- Molecular weight (if other than submission substance): 217.86
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): -----

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Chinese Academy of Science Laboratory Animal Center.
- Age at study initiation: 8 weeks of age
- Housing: housed in standard polyethylene cages, in groups of five per cage, with wood shavings as bedding
- Diet (e.g. ad libitum): rodent chow; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3C
- Humidity (%): 50% ± 15%
- Air changes (per hr): NA
- Photoperiod (hrs dark / hrs light): 12-h light-dark cycle;

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: DBA solution of different concentrations was prepared by dissolving DBA in deionized water and adjusting the pH to approximately 6.5 with 1N NaOH.
The DBA concentration is 500, 2000, and 5000 mg/l, respectively.
All the solutions were kept in the refrigerator at 4°C and were made up fresh every week.

DIET PREPARATION
- Rate of preparation of diet (frequency): Not available
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food: Not available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Not available
- Concentration in vehicle: Not available
- Amount of vehicle (if gavage): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available

Details on analytical verification of doses or concentrations:

Not Available

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0 (deionized water; vehicle control) or 5, 20, and 50 mg/kg body
Basis:
nominal in water

No. of animals per sex per dose:

Control: 5 males and 5 females
5 mg/kg: 5 males and 5 females
20 mg/kg: 5 males and 5 females
50 mg/kg: 5 males and 5 females

Control animals:

yes, concurrent vehicle

Details on study design:

Not Available

Examinations

Observations and examinations performed and frequency:

Not Available

Sacrifice and pathology:

GROSS PATHOLOGY & HISTOPATHOLOGY: NO Data

HISTOPATHOLOGY: Yes
The histopathological features observed by light and electron microscopy indicated that oral exposure to DBA may lead to morphological changes in the immune organs and that a number of immune cells in these organs had undergone apoptosis in male and female mice.

Other examinations:

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
Body weight was measured and recorded every 7 days
No significant differences in body weight were observed

Changes in Body Weights of Mice after 28-day Oral Exposure to DBA

DBA dosage
(mg /kg) Initial weight First week Second week Third week Fourth week
(A) Male
0 18.07 ± 0.61 20.75 ± 0.63 21.77 ± 0.68 22.35 ± 0.58 23.52 ± 0.56
5 18.01 ± 0.45 20.21 ± 0.51 21.40 ± 0.62 22.11 ± 0.54 23.05 ± 0.52
20 17.96 ± 0.51 20.48 ± 0.59 21.43 ± 0.76 21.54 ± 0.89 22.55 ± 0.94
50 17.94 ± 0.47 19.60 ± 0.70 20.69 ± 0.78 21.28 ± 0.96 21.97 ± 0.97
(A) Male
0 17.69 ± 0.46 19.36 ± 0.46 20.04 ± 0.55 20.33 ± 0.59 21.18 ± 0.62
5 17.79 ± 0.37 19.13 ± 0.55 19.77 ± 0.66 20.26 ± 0.63 21.08 ± 0.72
20 17.68 ± 0.32 18.77 ± 0.44 19.58 ± 0.52 19.94 ± 0.62 20.79 ± 0.59
50 17.73 ± 0.31 19.18 ± 0.42 19.97 ± 0.55 20.51 ± 0.55 21.29 ± 0.59

Note. Animals were treated by oral exposure to DBA for consecutive 28 days. Body weight (g) is the means ± SE (n ¼ 10 per group), p < 0.05,

Other:
Organ Weight:
the mean thymus weight and its relative weight were significantly reduced in male and female mice after dosing with 20 and 50 mg/kg DBA and the mean spleen weight and spleen relative weight were increased in the mice of both sexes in the group of 20 and the 50 mg/kg
The absolute number of cells harvested per spleen and thymus was significantly decreased in the group of 20 and 50 mg/kg

Statistics:

Not Available

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

No significant differences in body weight were observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The absolute number of cells harvested per spleen and thymus was significantly decreased in the group of 20 and 50 mg/kg

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

morphological changes were observed.

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

LOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant differences in body weight were observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Mice were treated daily with 0 (deionized water; vehicle control), 5, 20, or 50 mg/kg body weight of DBA solution by intragastric administration of 0.1 ml/10 g body weight for 28 consecutive days. The lowest-observed-effect level (LOEL) was found to be at 50 mg/kg-bw/day, based on changes in the organs and body weight.

Executive summary:

To assess the subacute toxicity ofDibromoacetic acid (DBA),male and female BALB/c mice weredailytreatedwith 0 (deionized water; vehicle control), 5, 20 or 50 mg/kg body weight of DBA solution, by oral gavage of 0.1 ml/10 g body weight for 28 consecutive days.No obvious physical changes such as morbidity, mortality, or alterations in body weight were observed in any treatment group. However, we found that the spleen weight of the mice was significantly increased, while thymus weight was decreased in the 20- and 50-mg/kg dose groups. Howeverthe lowest-observed-effect level (LOEL) was found to be 50 mg/kg-bw/day, based on changes in the organs and body weight.