Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guiedline study and GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD TG 407
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
content: 99.1 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMAL
- Age at study initiation: 5 weeks
- Weight at study initiation: male 173.6 g; female: 145.3 g
- Housing: in groups of 2 or 3
- Diet ad libitum
- Water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): >10 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on exposure:
male and female rats weere given the test item for 28 days once daily by gavage. The test item was suspended in poyethylene glycole 400
Details on analytical verification of doses or concentrations:
The formulation was prepared as needed taking into account the analytically determined stability of 8 days
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily
Duration of test:
30 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes, concurrent vehicle
Details on study design:
The test item was administered once daily by gavage to male and female Wistar rats in daily doses of 100, 300 and 1000 mg/kg bw/day suspended in polyethylene glycol 400. The administration volume was 5 ml/kg bw. the animals were observed for mortality and clinical signs, determination of hematology and clinical chemistry data. After termination of treatment animals were subjected to gross and histopathological examination
Statistics:
Dunnett, U-test, Het-Dunn ( Dunnett exact test heterogeneous test)

Results and discussion

Effect levels

Dose descriptor:
other: NOAEL (reproductive organs)
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: The effects seen in male seminal vesicle at 1000 mg/kg bw/day are evaluated unspecific and stress related; an adverse effect is not assumed; females are without pathological findings.

Observed effects

At necropsy there was no evidence at any gross finding that had to be attributed to dosing with the test compound.
Histopathology revealed minimally or slightly reduced secretion in the seminal vesicles in 3 out of 5 males at 1000 mg/kg which was not
associated with degeneration. Changes in other male genital organs
(testes, epididymides, prostate or coagulation glands) could not be found
up to and including 1000 mg/kg. Thus, reduced secretion is regarded as unspecific and possibly stress—related. An adverse effect is not assumed.

Applicant's summary and conclusion

Executive summary:

The Macrolex Rot EG was administered once daily by gavage to male and female Wistar rats in daily doses of 100, 300 and 1000 mg/kg bw/day suspended in polyethylene glycol 400. The administration volume was 5 ml/kg bw. The animals were observed for mortality and clinical signs, determination of hematology and clinical chemistry data. After termination of treatment animals were subjected to gross and histopathological examination.

For general toxicity see the respective section for repeated dose toxicity.

At necropsy there was no evidence at any gross finding that had to be attributed to dosing with the test compound.

Histopathology revealed minimally or slightly reduced secretion in the seminal vesicles in 3 out of 5 males at 1000 mg/kg which was not associated with degeneration. Changes in other male genital organs (testes, epididymides, prostate or coagulation glands) could not be found up to and including 1000 mg/kg. Thus, reduced secretion is regarded as unspecific and possibly stress—related. An adverse effect is not assumed. Therefore, an overall NOAEL (reproductive organs) = 1000 mg/kg bw/day was established.