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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Name : Cyclamen Aldehyde
CAS # : 103-95-7
CAS name : Benzenepropanal, α-methyl-4-(1-methylethyl)-
EC # : 203-161-1
EC name : 3-p-cumenyl-2methylpropionaldehyde
IUPAC name : 2-methyl-3-[4-(propan-2-yl)phenyl]propanal

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Rabbits were administered the test substance, Cyclamen Aldehyde, and/or the control article, corn oil, formulations orally (stomach tube) once daily on Day 1 of study (DS 1) to 14.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
14 days
Frequency of treatment:
once per day
Duration of test:
14 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
30 mg/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
100 mg/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
300 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
5 male
0 female
Control animals:
yes, concurrent vehicle
Details on study design:
The objective of this study was to determine the potential toxicity of Cyclamen Aldehyde, when given orally via stomach tube for 14 consecutive days to male New Zealand White rabbits. In addition, potential effects on the male reproductive organs, including sperm parameters were assessed.
The study design was as follows:
Rabbits were administered the test substance, Cyclamen Aldehyde, and/or the control article, corn oil, formulations orally (stomach tube) once daily on Day 1 of study (DS 1) to 14.
The following parameters and endpoints were evaluated in this study: viability, clinical signs, body weights, body weight changes, food consumption, gross and microscopic pathology, sperm evaluations (motility, count, and morphology), and organ weights. Urine samples were collected from all rabbits on Day 15 prior to euthanasia for possible future evaluation.

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male

Observed effects

All rabbits survived to scheduled euthanasia. None of the clinical signs that occurred were attributed to oral administration of Cyclamen Aldehyde, and all rabbits appeared normal at necropsy examination.
Body weights, body weight gains and food consumption values (g/day and g/kg/day) were comparable among the groups and were unaffected by dosages of Cyclamen Aldehyde as high as 300 mg/kg/day.
Cyclamen Aldehyde did not affect the weights of the reproductive (testes, epididymides, seminal vesicles [with and without fluid] or prostate) or non-reproductive (liver or kidneys) at any dosage level. There were no microscopic findings in the testes or epididymides at 300 mg/kg/day. In addition, there were no noteworthy changes in sperm motility (number and percentage of motile sperm or nonmotile sperm from ejaculated semen samples), sperm concentration (total and cauda epididymal sperm count and density) or sperm morphology at any dosage level.

Organ Weights
Terminal body weights were comparable among the four dosage groups. The weights of the epididymides, left cauda epididymis, testes, seminal vesicles (with and without fluid) and prostate and the ratios of these organ weights to terminal body weight were unaffected by dosages cyclamen aldehyde as high as 300 mg/kg/day.
In addition, there were no test substance-related changes in the non-reproductive organs (i.e., liver or paired kidneys) at any dosage level. There were no patterns, trends, or correlating data to suggest these values were toxicologically relevant. The apparent increase in the absolute and relative (% body weight) weights of the liver that occurred at 300 mg/kg/day (18% and 21% over controls, respectively) was largely attributed to one rabbit (no. 8596) in the 300 mg/kg/day dosage group with an absolute liver weight of 111.1 g (range: 70.1 to 92.3 for other rabbits in the group). Exclusion of this rabbit from summarization would still result in a higher group mean weight in comparison to the control group value. The absolute and relative (% body weight) weights of the paired kidneys were also increased in the 300 mg/kg/day dosage group (1 1% and 13% over controls, respectively), again attributed to one rabbit (no. 8595) in this dosage group. Overall, the individual organ weight differences observed were considered incidental and unrelated to administration of cyclamen aldehyde.

Sperm Evaluations
The values for the number of motile sperm and total sperm count from ejaculated semen samples were highly variable across the dosage groups, including the control group. Whilst a slight trend in the mean number of motile sperm (596.6, 543.3 and 431.0 in the 30, 100 and 300 mg/kg/day dosage groups, respectively, vs. 627.0 in controls) and total sperm count (616.6, 595.5 and 496.2 in the 30, 100 and 300 mg/kg/day dosage groups, respectively, vs. 679.0 in controls) from ejaculated samples in the cyclamen aldehyde-treated groups was observed, individual values were highly variable and the lowest reported individual values were within the range of the control group values. In general, all values across all treated groups were within the range of the concurrent control group values and/or the historical control range at the Testing Facility. The observed trend in sperm motility and total sperm count was not considered an adverse finding of Cyclamen Aldehyde.
Values for percent motile sperm, number of nonmotile sperm from the semen ejaculate sample and cauda epididymal sperm count and density were comparable among the four dosage groups.
In addition, there were no patterns or trends in the morphology data to suggest any toxicological relevance.

Applicant's summary and conclusion

Conclusions:
Cyclamen Aldehyde was administered orally to male rabbits for 14 days at dosages as high as 300 mg/kg/day. There were no noteworthy changes in reproductive organs, non-reproductive organs or sperm parameters were observed.
Executive summary:

Cyclamen Aldehyde when administered orally to male rabbits for 14 days at dosages as high as 300 mg/kg/day did not produce any clinical observations, changes in body weight or food consumption or affect the weights of any reproductive or non-reproductive organs that were evaluated. There were no microscopic findings in the testes or epididymides at 300 mg/kg/day, and no noteworthy changes in sperm parameters were observed.