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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
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)
- Related CAS number: 1318-02-1
- Analytical purity: no data

Test animals

Species:
rat
Strain:
other: COX-SD
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

Maternal 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.
Ovaries and uterine content:
see. maternal examinations

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Remarks:
Generation P
Effect level:
>= 2 other: %
Basis for effect level:
other: effect type not specified

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Conclusions:
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.