Registration Dossier

Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
no data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Few information on study design but the method is relevant.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1988
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In the in vivo study an single dose of the Trifluoroacetic acid was administered to male rats by oral route. 3 days after the treatment, the testes were removed for histopathological observations.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Trifluoroacetic acid
EC Number:
200-929-3
EC Name:
Trifluoroacetic acid
Cas Number:
76-05-1
Molecular formula:
C2HF3O2
IUPAC Name:
trifluoroacetic acid
Details on test material:
- Name of test material (as cited in study report): Trifluoroacetic acid (TFAA)
- Physical state: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: assumed to be stable during the test (sponsor responsibility)
- Storage condition of test material: no data
- Other: Source: Sigma (Poole, Dorset, UK)

Test animals

Species:
rat
Strain:
other: Alpk/AP (Wistar derived)
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: (P) x10 wks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: rats were housed in polycarbonate and metal cages
- Use of restrainers for preventing ingestion (if dermal): not applicable
- Diet (e.g. ad libitum): PCD Diet (Special Diet services, Essex, UK), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 50 (+/-10%)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

IN-LIFE DATES: From: To: no data

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: the pH of the tested solution is adjusted to 7 using 1.0 M NaOH

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

VEHICLE: no data
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Lot/batch no. (if required):
- Purity:
Details on mating procedure:
not applicable: no mating experiment was performed
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not applicable
Duration of treatment / exposure:
single dose
Details on study schedule:
not applicable
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10 and 25 mg/kg bw
Basis:
nominal in water
in 5 mL water/kg bw, adjusted to pH 7 using 1.0 M NaOH
No. of animals per sex per dose:
10 males/dose
Control animals:
yes, concurrent vehicle
Details on study design:
no details
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: the body weight was determined at the moment of the sacrifice of the animals.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

Oestrous cyclicity (parental animals):
not applicable
Sperm parameters (parental animals):
Parameters examined in male parental generations:
testis weight, stages of spermatogenesis (based on the classification of Leblond and Clermont)
Litter observations:
not applicable
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: 5 animals were anesthetized for removing of testis 3 days after the administration of the test item. The remaining animals were sacrificed (no data on the time of the sacrifice)
- Maternal animals:not applicable

GROSS NECROPSY: no data
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGHTS
Testes were removed and processed into glycol methacrylate. 2 µm sections were cut and stained with hematoxylin and eosin and with the periodic acid-Schiff technique for the demonstration of the spermatid acrosome. Definition of the stages of spermatogenesis was based on the classification of Leblond and Clermont.
Postmortem examinations (offspring):
not applicable
Statistics:
data were evaluated by analysis of variance followed by student's t test, taking p<0.05 as the level of significance.
Reproductive indices:
not applicable
Offspring viability indices:
not applicable

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Description (incidence and severity):
not applicable
Reproductive function: sperm measures:
not examined
Description (incidence and severity):
not applicable
Reproductive performance:
not examined
Description (incidence and severity):
not applicable

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): over a period of 3 days after dosing the animal appeared healthy.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): no effects

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS): no data

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): not examined

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): not examined

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): not examined

ORGAN WEIGHTS (PARENTAL ANIMALS): no effects

GROSS PATHOLOGY (PARENTAL ANIMALS): not examined

HISTOPATHOLOGY (PARENTAL ANIMALS):no effects

OTHER FINDINGS (PARENTAL ANIMALS): no data

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks:
fertility
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: overall effects

Results: F1 generation

General toxicity (F1)

Clinical signs:
not examined
Description (incidence and severity):
not applicable
Mortality / viability:
not examined
Description (incidence and severity):
not applicable
Body weight and weight changes:
not examined
Description (incidence and severity):
not applicable
Sexual maturation:
not examined
Description (incidence and severity):
not applicable
Organ weight findings including organ / body weight ratios:
not examined
Description (incidence and severity):
not applicable
Gross pathological findings:
not examined
Description (incidence and severity):
not aplicable
Histopathological findings:
not examined
Description (incidence and severity):
not applicable

Details on results (F1)

not applicable

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

not applicable

Applicant's summary and conclusion

Conclusions:
Under the test conditions, Trifluoroacetic acid administered by oral route in a single dose had no effect on the fertility of male rats.
Executive summary:

In a fertility study trifluoroacetic acid (TFA; 99% purity) was administered to wistar derived male rats (10 males/dose) in water by oral route at dose levels of 0, 10, 25 mg/kg bw. The test item was diluted in 5 mL of water. Three days after the administration of the test item, testes were removed under anaesthesia in 5 animals per group and examined for histopathology. The remaining 5 animals were sacrificed to measure the organ and the body weight.

 

Trifluoroacetaldehyde (TFAld) and Trifluorothanol (TFE) were administered at the same doses in parallel groups in order to compare the effects between the different substance.

No effect on the testis weight and on the spermatogenesis was observed in the TFA groups at both doses. For information, a significant decrease in the testis relative weight was observed in the TFE groups at both doses. The effects on the spermatogenesis were also recorded including a partial loss of spermatogonia and early spermatocytes in stages IV and V. Similar effects were observed in the TFAld groups while no effect were noted in the TFA groups.

Under the test conditions, trifluoroacetic acid administered by oral route in a single dose had no effect on the fertility of male rats at the contrary to the TFE and the TFAld as the parent compounds of the TFA. In fact, TFA is the final metabolite of TFE and TFAld as already determined in several toxicokinetic studies (see § 7.1).

 

This study, focused on testes as a target, is scientifically acceptable even if there is a lack of information on the study design and on the results.