Registration Dossier

Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
three-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from EFSA journal.

Data source

Reference
Reference Type:
review article or handbook
Title:
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)
Author:
European Food Safety Authority (EFSA), Parma, Italy
Year:
2015
Bibliographic source:
EFSA Journal 2015;13(7):4152

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: as mention below
Principles of method if other than guideline:
Higher doses of test chemical were administered in animals of three generation to examine the reproductive parameters.
GLP compliance:
no
Limit test:
yes
Justification for study design:
No Data Available

Test material

Constituent 1
Chemical structure
Reference substance name:
Sorbitan monostearate, ethoxylated
EC Number:
500-020-4
EC Name:
Sorbitan monostearate, ethoxylated
Cas Number:
9005-67-8
Molecular formula:
C64-H126-O26 Unspecified
IUPAC Name:
Sorbitan monostearate, ethoxylated
Test material form:
not specified
Details on test material:
Details on test material
- Name of test material (as cited in study report): Polysorbate 60
- Molecular formula (if other than submission substance): C64-H126-O26
- Molecular weight (if other than submission substance): 606.8318 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available
Specific details on test material used for the study:
- Molecular weight (if other than submission substance): 606.8318 g/mol
- Substance type: Organic
- Physical state: No Data Available
- Impurities (identity and concentrations): No Data Available

Test animals

Species:
mouse
Strain:
other: C57BL/6
Details on species / strain selection:
No Data Available
Sex:
male/female
Details on test animals or test system and environmental conditions:
No Data Available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on exposure:
No data available
Details on mating procedure:
Four matings were performed in the F0 and F1 generations and three matings in the F2 generation.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Duration of treatment / exposure:
No data available
Frequency of treatment:
No data available
Details on study schedule:
test chemical (equivalent to 0 or 5 g/kg bw/day; higher doses expected in pregnant females and in the post-weaning period of 10 g/kg bw/day).
Doses / concentrations
Remarks:
5000mg/kgbw/day
10000mg/kg bw/day (post weaning period)
No. of animals per sex per dose:
No data
Control animals:
yes
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
No data available
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
No data available
Postmortem examinations (offspring):
No data available
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effects on body weight gain of pregnant mice were found
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Description (incidence and severity):
No effects on sperm motility were found
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
lactation index decreased.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
5 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive function (sperm measures)
other: no effects on weight of male gonads
Remarks on result:
other: not specified

Target system / organ toxicity (P0)

Critical effects observed:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P1)

Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (P1)

Critical effects observed:
not specified
System:
other: not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
the no. of lice pus biorn, viability index decreased
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Pup weight at weaning was significantly reduced after exposure to test chemical
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
lactation index decreased.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Effect levels (F1)

Dose descriptor:
LOAEL
Generation:
F1
Effect level:
5 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
other: Lactation index decreased
Remarks on result:
other: not specified

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Dose descriptor:
other: not specified
Generation:
other: not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F2)

Critical effects observed:
not specified
System:
other: not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEL for the test chemical in male and female C57BL/6 was observed to be 5000mg/kg F0 genearation and LOAEL for F1 generation observed to be 5000mg/kg
Executive summary:

In the three generations of male and female C57BL/6 mice, continuously, a diet containing10 % test chemical (equivalent to 0 or 5 g/kg bw/day; higher doses expected in pregnant females and in the post-weaning period of 10 g/kg bw/day). Four matings were performed in the F0 and F1 generations and three matings in the F2 generation. Pup weight at weaning was significantly reduced after exposure to both polysorbates. The number of live pups born, the viability index and the lactation index decreased. No effects on body weight gain of pregnant mice were observed, and no effects on organ weights of gonads or sperm motility were recorded. From the observations, The NOAEL for the test chemical in male and female C57BL/6 was observed to be 5000mg/kg in F0 genearation and LOAEL for F1 generation observed to be 5000mg/kg

Categories Display