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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 2014
Reliability:
1 (reliable without restriction)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Synthetic squalane

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
Wistar Hannover RccHan®:WIST rats
Sex:
male/female
Details on test animals and environmental conditions:
The females were nulliparous and nonpregnant
Cage card and individual ear tattoo
Acclimatization: 7 days (males) and 6 days (females) between arrival and treatment start

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Males: two weeks prior to mating and at least up to and including the day before sacrifice (minimum of 28 days).
Females: two weeks prior to mating and at least up to and including the day before sacrifice (day 4 postpartum).
Frequency of treatment:
Once daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Group 1
Dose / conc.:
100 mg/kg bw/day (nominal)
Remarks:
Group 2
Dose / conc.:
300 mg/kg bw/day (nominal)
Remarks:
Group 3
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
Group 4
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Sacrifice and pathology:
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Other examinations:
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Statistics:
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Mortality:
no mortality observed
Description (incidence):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Ophthalmological findings:
not specified
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Urinalysis findings:
no effects observed
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Behaviour (functional findings):
effects observed, non-treatment-related
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Neuropathological findings:
not specified
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Histopathological findings: neoplastic:
not specified
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Other effects:
not specified
Description (incidence and severity):
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record
Details on results:
Kindly refer to General toxicity of Parental (F0) and litter (F1) generation in reprotoxicity OECD 422 study record

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
ca. 10 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
food efficiency
water consumption and compound intake
haematology
clinical biochemistry
urinalysis
behaviour (functional findings)
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
For F0 generation:

Males:
The dose of 1000 mg/kg can be considered the NOAEL (No Observed Adverse Effect Level) for systemic toxicity.
The dose of 1000 mg/kg can be considered the NOEL (No Observed Effect Level) for fertility and mating performance.
Females:
The dose of 1000 mg/kg can be considered the NOAEL for systemic toxicity.
The dose of 1000 mg/kg can be considered the NOAEL for fertility and mating performance and 100mg/kg for breeding.

For F1 generation: The dose of 1000 mg/kg can be considered the NOEL.
Executive summary:

The study was designed to investigate the systemic toxicity and potential adverse effects of the test item on reproduction (including offspring development) and is compatible with the requirements of the OECD Guidelines for Testing of Chemicals No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test” (adopted 22 March 1996).

The test item Phytosqualan was administered orally (by gavage) to three groups, each consisting of ten male and ten female RccHan®:WIST rats, daily for at least 4 weeks (including two weeks prior to mating, through mating, pregnancy and early lactation for females) at the following dose levels: 0, 100,300 and 1000 mg/kg/day.

No mortality was recorded in any sex. No test-item-related differences from the control group were recorded in males. No test item-related alterations were recorded.

The systemic toxicity NOAEL was 1000 mg/kg/day for male and female (F0 and F1 generation)