methyl (2E)-[2-(chloromethyl)phenyl](methoxyimino)acetate

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study report which meets basic scientific principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Principles of method if other than guideline:

see details in remarks on amterial and methods

GLP compliance:

yes

Remarks:

BASF AG, Experimental Toxicology and Ecology

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): 520 F-Chlormethyloximether
- Physical state: solid/ dark green
- Analytical purity: 96.8%
- Lot/batch No.: 31196-182
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH
- Age at study initiation: 42 ± 1 days
- Weight at study initiation:
- Housing: 5 per cage
- Diet (e.g. ad libitum): Kliba maintenance diet
- Water (e.g. ad libitum): drinking water (from water bottles)
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

DIET PREPARATION
- For each concentration, the test substance was weighed out and mixed with a small amount of food. Then corresponding amounts of food, depending on test group, were added to this premix in order to obtain the desired concentrations. Mixing was carried out for about 10 minutes in a laboratory mixer.
- Rate of preparation of diet (frequency): every 4 weeks

Details on mating procedure:

not done

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Mean values of 520 F-Chlormethyloximether in Kliba lab diet were found to be in the range of 97.7 – 108.2% of the nominal concentration.

Duration of treatment / exposure:

90 days

Frequency of treatment:

continously, 7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 250, 1250 and 5000 ppm (males); 0, 250, 1250 and 2500 ppm (females)
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
16.2, 77.6 and 326.3 mg/kg bw/d (males); 18.3, 93.4 and 191.3 mg/kg bw/d (females)
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- A check for moribund and dead animals was made twice daily on working days and once daily on Saturdays, Sundays and public holidays. If animals were in a moribund state, they were sacrificed and necropsied. All animals were checked daily for any clinically abnormal signs.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: prior to the administration period (day 0) and thereafter at weekly intervals
- The following parameters were examined: abnormal behavior during “handling”, fur, skin, posture, salivation, respiration, activity/arousal level, tremors, convulsions, abnormal movements, impairment of gait, lacrimation, palpebral closure, exophthalmus,feces (appearance/consistency), urine, pupil size


BODY WEIGHT: Yes
- Time schedule for examinations: day 0 (start of the administration period) and thereafter at weekly intervals


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily (Group water consumption)

Oestrous cyclicity (parental animals):

Vaginal smears were prepared for cycle determination in the morning and evaluated according to the timetable. The differentiation was conducted according to the Table 1.

Sperm parameters (parental animals):

Parameters examined in [P] male parental generations:
[testis weight, epididymis weight, sperm count in testes, sperm count in epididymides, sperm motility, sperm morphology]

Litter observations:

not done

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals
- Maternal animals: All surviving animals


GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]


HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues weighed were: Liver, Kidneys, Adrenal glands, Testes, Epididymides, Cauda epididymides, Ovaries, Uterus, Prostate, Seminal vesicles including coagulation glands, Spleen, Brain, Heart, Thymus, Thyroid glands. The following organs or tissues were fixed in 4% formaldehyde solution: All gross lesions, Brain, Pituitary gland, Thyroid glands, Parathyroid glands, Oesophagus, Salivary glands (mandibular and sublingual glands), Trachea, Lungs, Pharynx, Larynx, Nose (nasal cavity), Thymus, Aorta, Heart, Liver, Pancreas, Spleen, Kidneys, Adrenal glands, Oviducts, uterus and vagina, Prostate and seminal vesicles including coagulation glands, Stomach (forestomach and glandular stomach), Duodenum, jejunum and ileum, Cecum, colon and rectum, Urinary bladder, Lymph nodes (mesenteric and axillary lymph nodes), Sciatic nerve, Bone marrow (femur), Eyes, Extraorbital lacrimal glands, Skin, Female mammary gland, Spinal cord (cervical, thoracic and lumbar cords), Sternum with marrow, Femur with knee joint, Skeletal muscle

Postmortem examinations (offspring):

not done

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): no mortality or clinical signs were observed.


BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): body weight (-11.7% on day 91) as well as body weight change (-20.5% on day 91) were significantly impaired only in the male animals of high dose group (5000 ppm) throughout the whole study period. No substance-related changes in food consumption were observed.


TEST SUBSTANCE INTAKE (PARENTAL ANIMALS): The approximate mean daily test-substance intake in mg/kg bw/day in males of the 250, 1250 and 5000 ppm dose groups were 16.2, 77.6 and 326.3, respectively. The approximate mean daily test-substance intake in mg/kg bw/day in females of the 250, 1250 and 2500 ppm dose groups were 18.3, 93.4 and 191.3, respectively.


REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): No substance-related effects were observed.


REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): There were no treatment-related changes in the sperm parameters measured.


ORGAN WEIGHTS (PARENTAL ANIMALS): The only treatment-related effect observed was decrease of the terminal body weight in the 5000 ppm group males (88 % in comparison to controls)


GROSS PATHOLOGY (PARENTAL ANIMALS): incidentally as single cases were reported which were not substance-related findings.


HISTOPATHOLOGY (PARENTAL ANIMALS): no substance-related findings were observed

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

ca. 191.3 mg/kg bw/day (actual dose received)

Sex:

female

Basis for effect level:

other: no effects

2

Dose descriptor:

NOAEL

Effect level:

ca. 326.3 mg/kg bw/day (actual dose received)

Sex:

male

Basis for effect level:

other: no effects

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

The oral administration of 520 F-Chlormethyloximether via the diet over a period of 3 months caused no adverse effects on the fertility parameters in both males and females up to be the highest dose tested.