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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Follow up to repeated dose toxicity study to investigate the potential urogenital toxic effect
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles - acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Principles of method if other than guideline:
A special designed follow-up study on the potential urogenital toxic effect seen in the P&G study on UDL-738 (Scientific Associates, Inc., 1975, Nr. R-12888)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): UDL-1078 (P&G code)
- Chemical name: Zeolite, cuboidal, crystalline, synthetic, non-fibrous
- Framework: cuboidal
- Related CAS number: 1318-02-1
- Analytical purity: no data

Test animals

Species:
rat
Strain:
other: COX-SD
Sex:
male
Details on test animals and environmental conditions:
40 animals/group (individually housed) were treated with the appropriate test substance concentration.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on exposure:
- diet: Purina laboratory Chow (meal)
- prepared weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
160 or 200 d
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.125, or 2.0 %
Basis:
nominal in diet
No. of animals per sex per dose:
40
Control animals:
yes

Examinations

Parental animals: Observations and examinations:
A daily examination (general appearance, mortality; other toxic signs) was performed throughout the entire study. Feed consumption and weight were recorded weekly. Urine analyses, consisting of urobilin, urobilinogen, albumin, acetone, bilirubin, color, occult blood, glucose, specific gravity, pH, appearance, red blood cells, white blood cells, casts, crystals, spermatozoa, and epithelial cells was conducted on each surviving animal; bacteriological analyses of the urine were conducted at day 0, 45, and 90. At day 90 of the study, all surviving animals were anesthetized and a whole body X-ray was made (dorsal ventral plain to evaluate the genital urinary system.
Postmortem examinations (parental animals):
From the groups, representative males were selected at random and sacrificed at day 160. The remaining 19 animals per group were exposed to the test substance until day 200 of the study when sacrificed.
Gross pathology and necropsy were performed:
Special attention was turned on the urogenital system beside following tissues:
adrenal gland, bone, bone marrow, brain, pituitary, gonads, heart, small intestine, large intestine, liver, lung, lymph nodes, pancreas, spleen, stomach, thyroid gland, skin, trachea, esophagus, salivary glands, eyes, tongue, seminal vesicles, prostate, bladder.

Results and discussion

Results: P0 (first parental animals)

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
Gross pathological findings:
no effects observed

Details on results (P0)

Body weights, feed consumption and weight gain were comparable to control. No gross signs of adverse systemic effect due to the ingestion of the test material were observed in any of the animals.
Compound consumption was determined as follows:
0 mg/kg bw/day (control), 75.14 mg/kg bw/day (0.125%), 1250.79 mg/kg bw/day (2%).

For observations of bladder and kidney pathology see chapter 7.5

Animals sacrificed during the study due to physiological problems:
Gross necropsy of one (succumbed on day 158 of study) out of three control animal showed congested testes and the ductus deferens appeared enlarged. One control animal succumbed on day 148 revealed severely congested prostate.

Gross necropsy of the four animals in Group II (0.125%), which were sacrificed on an unscheduled basis, revealed testes without pathological findings.

160-Day interim sacrifice:
---------------------------
At gross necropsy (160 days) the testes of the control group appeared normal.
Gross necropsy of the animals of Group II (0.125%) showed findings which were generally unremarkable. One male animal with right testis approximately 1/3 the expected normal size was observed.
Gross necropsy of the animals of Group III (2%) sacrificed at 160-days, revealed no effects on the testes.

200-Day Terminal Sacrifice:
----------------------------
Gross necropsy of the animals in Group I (controls) showed testes without findings.
Gross necropsy of the animals, of Group II ( 0.125%) showed findings which were generally unremarkable (testes without findings).
Gross necropsy of the animals of Group III (2%), showed findings which were generally unremarkable; one animal had small seminal vesicles.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 2 other: %
Based on:
test mat.
Sex:
male
Basis for effect level:
other: testes

Results: F1 generation

Effect levels (F1)

Remarks on result:
other: The available study is a follow up to repeated dose toxicity study to investigate the potential urogenital toxic effect in males, therefore no F1 generation exists.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No treatment related effects on the testes of the rats were observed up to and including 2.0% corresponding to 1250.79 mg test substance/kg bw/day.

Applicant's summary and conclusion