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EC number: 266-037-1 | CAS number: 65997-01-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 999
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Deviations:
- yes
- Remarks:
- Additional obs of oestrous cycling, sexual maturation & histo examinations. No total cauda epididymal sperm no., % progressively mobile sperm, % progressively motile sperm, % morphologically normal sperm & % of sperm with each identified abnormality
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Stigmast-5-en-3-β-ol
- EC Number:
- 201-480-6
- EC Name:
- Stigmast-5-en-3-β-ol
- Cas Number:
- 83-46-5
- Molecular formula:
- C29H50O
- Reference substance name:
- (24R)-ergost-5-en-3β-ol
- EC Number:
- 207-484-4
- EC Name:
- (24R)-ergost-5-en-3β-ol
- Cas Number:
- 474-62-4
- Molecular formula:
- C28H48O
- IUPAC Name:
- (3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R)-5,6-dimethylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
- Reference substance name:
- Stigmasta-5,22-dien-3-β-ol
- EC Number:
- 201-482-7
- EC Name:
- Stigmasta-5,22-dien-3-β-ol
- Cas Number:
- 83-48-7
- Molecular formula:
- C29H48O
- IUPAC Name:
- (3S,8S,9S,10R,13R,14S,17R)-17-[(E,2R,5S)-5-ethyl-6-methylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
- Reference substance name:
- Linoleic acid
- EC Number:
- 200-470-9
- EC Name:
- Linoleic acid
- Cas Number:
- 60-33-3
- Molecular formula:
- C18H32O2
- IUPAC Name:
- octadeca-9,12-dienoic acid
Constituent 1
Constituent 2
Constituent 3
Constituent 4
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Germany.
- Females, nulliparous and non-pregnant: yes
- Age at study initiation: (P) 4-5 x weeks (on receipt); (F1) x weeks
- Weight at study initiation: (P) Males: approx. 210 g; Females: approx. 125 g; (F1) Males: approx. 125 g; Females: approx. 112.5 g
- Fasting period before study: No data
- Housing: suspended stainless-steel group cages each with a wire mesh floor and front.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 40-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: No data
Administration / exposure
- Route of administration:
- oral: feed
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): At least every four weeks.
- Mixing appropriate amounts with (Type of food): Commercial rodent diet.
- Storage temperature of food: 2-10°C - Details on mating procedure:
- At the end of the 10 week premating period:
- M/F ratio per cage: 1:1
- Length of cohabitation: three weeks
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy.
- The mated F0 females were housed individually in suspended wire mesh cages with wire mesh floor and front.
- mated males were returned to their group cages (four animals per cage). - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Several batches of diet were analysed to study homogeneity, stability and content of phytosterol ester.
Phytosterol ester was extracted from the diet with petroleum ether. The concentration of phytosterol ester in thc extracts was determined using HPLC with diode array detection (DAD) at 210 nm. Quantification of phytosterol ester was obtained by comparing the areas of the phytosterol peaks in the samples with those of calibration solutions containing known amounts of phytosterol ester. - Duration of treatment / exposure:
- Approximately 32 weeks of treatment
- Frequency of treatment:
- Continuous in diet
- Details on study schedule:
- - F1 parental animals not mated until 12 weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: at least 15 weeks.
The same procedure was used for the F1 to F2 generation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1.6 other: % (w/w) phytosterol ester
- Remarks:
- Equivalent to a concentration of 1.0% (w/w) phytosterol
- Dose / conc.:
- 3.2 other: % (w/w) phytosterol ester
- Remarks:
- Equivalent to a concentration of 2.0% (w/w) phytosterol
- Dose / conc.:
- 8.1 other: % (w/w) phytosterol ester
- Remarks:
- Equivalent to a concentration of 5.0% (w/w) phytosterol.
Equivalent to 2500-9100 mg/kg bw/day phytosterol ester.
Equivalent to 1540-5620 mg/kg bw/day phytosterol.
- No. of animals per sex per dose:
- 28
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: Dose used was the same as previously conducted 90-day dietary study.
- Rationale for animal assignment (if not random): Random
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly for all animals in the premating period; males weekly thereafter; females on gestation days 0, 7, 14 and 21 and lactation days 1, 7, 14 and 21.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION: No - Oestrous cyclicity (parental animals):
- Approximately one week after weaning of their pups, vaginal smears were made from the F0 females for 14 consecutive days. In the F1 animals vaginal opening was scored on post natal day 39.
- Sperm parameters (parental animals):
- Parameters examined in F0 and F1 male parental generations: testis weight, epididymis weight, prostate weight, seminal vesicles weight, preputial separation was scored in F1 animals on post natal day 31.
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 ] offspring: number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities.
GROSS EXAMINATION OF DEAD PUPS: yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: none
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY: none - Postmortem examinations (parental animals):
- SACRIFICE
At or shortly after weaning 10 male and 10 female F0 and F1 pups per group were subjected to a thorough necropsy. The following tissues were preserved for microscopic examination: ovaries, uterus, vagina, testes, epididymides, seminal vesicles (with coagulating glands and their fluids), prostate, pituitary, adrenals, liver and organs or tissues showing macroscopic abnormalities.
At termination all surviving parent animals of the F0 and F1 generations were killed and the following organs and tissues preserved for microscopic examination: adrenals.
brain, epididymides, liver, ovaries, pituitary, prostate, seminal vesicles with coagulating glands, testes, uterus with cervix (after counting implantation sites), vagina and all gross lesions. - Postmortem examinations (offspring):
- On post natal day 21, the F1 pups were weaned and shortly after 28 males and 28 females were selected at random from as many litters as possible in each group to produce the next generation - these animals were approximately 5 weeks old at the beginning of the F1 premating period. Mating of siblings was avoided. From the remaining F1 pups, 10 male and 10 female pups were necropsied thoroughly. The remaining pups were sacrificed after an external examination only. The same procedure was used for the F2 generation.
- Statistics:
- Body weight, food consumption and food efficiency data were subjected to one way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. Fisher's exact probability test was used to evaluate the numbers of mated and pregnant females, females with liveborn pups, females surviving delivery, females with (all) stillborn pups. live born and stillborn pups, pups lost at various stages, pups surviving 21 days, and male pups on postnatal days 1 and 21. Duration of gestation, litter size, and number of implantation sites per litter were evaluated by Kruskal Wallis non-parametric analysis of variance followed by Mann-Whitney U test. For evaluation of the incidence of pathological changes and clinical signs, Fisher's exact probability test was used. The time of achievement of preputial separation and vaginal opening was analysed with ANOVA followed by Dunnett's multiple comparison test. The chi -square test was used to evaluate the length of oestrus.
- Reproductive indices:
- For the assessment of fertility and reproductive performance the mating, fertility, fecundity, gestation and live births indices were calculated, and the sex ratio of pups was determined.
- Offspring viability indices:
- Viability and lactation indices were calculated.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No further details available.
- Mortality:
- no mortality observed
- Description (incidence):
- No further details available.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Males: decreases were observed in weeks 2-7 and on occasions in weeks 5-15 and 18-19 in the high dose group.
Females: no statistically significant differences. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were inconsistent differences (increases and decreases) between control and treated groups.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment-related observations (no further details available).
- Histopathological findings: neoplastic:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 8.1 other: % (w/w) phytosterol ester; equivalent to 2500-9100 mg/kg bw/day phytosterol ester, or 1540-5620 mg/kg bw/day phytosterol
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No further details available.
- Mortality:
- no mortality observed
- Description (incidence):
- No further details available.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Males: decreases were observed in weeks 2-7 and on occasions in weeks 5-15 and 18-19 in the high dose group, and decreases in weeks 6-9 and 11-14 of the low dose group. These changes were statistically significant.
Females: no statistically significant differences, except for day 7 of lactation in the high dose F1 generation. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were inconsistent differences (increases and decreases) between control and treated groups.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In males there was a small but statistically significant increase in the relative brain weight in low and mid dose groups only.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No further details available.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No further details available.
- Histopathological findings: neoplastic:
- not examined
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P1)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 8.1 other: % (w/w) phytosterol ester; equivalent to 2500-9100 mg/kg bw/day phytosterol ester or 1540-5620 phytosterol
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (P1)
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No further details available.
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- Pup mortality was increased on post natal day 4. Although the differences reached statistical significance, the values were within the historical control limits.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No further details available.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was an inconsistent pattern of food consumption. The findings were not adverse.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 8.1 other: % (w/w) phytosterol ester; equivalent to 2500-9100 mg/kg bw/day phytosterol ester and 1540-5620 mg/kg bw/day phytosterol
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F1)
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- Pup mortality was increased in the mid and high dose groups compared with the controls; however, the values fell within the historical control limits.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Effect levels (F2)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- >= 8.1 other: % (w/w) phytosterol ester; equivalent to 2500-9100 mg/kg bw/day phytosterol ester and 1540-5620 mg/kg bw/day phytosterol
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F2)
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 1 Intake of phytosterol ester in parent animals
Phytosterol esters (% in diet) | |||||
Generation | Sex | Period | 1.6 | 3.2 | 8.1 |
Phytosterol ester (g/kg bw/day) | |||||
F0 | Males | Premating weeks 1 -10 | 0.9 -0.5 | 1.8 -1.6 | 4.4 -2.7 |
Females | Premating weeks 1 -10 | 1.1 -0.6 | 2.1 -1.3 | 5.6 -3.4 | |
Gestation week 1 | 0.8 | 1.5 | 3.8 | ||
Gestation week 2 | 0.8 | 1.5 | 3.9 | ||
Gestation week 3 | 0.5 | 1.0 | 2.5 | ||
Lactation week 1 | 1.1 | 2.1 | 5.7 | ||
Lactation week 2 | 1.8 | 3.5 | 9.1 | ||
Lactation week 3* | 2.3 | 4.5 | 12.6 | ||
F1 | Males | Premating weeks 1 -10 | 1.3 -0.6 | 2.6 -1.1 | 6.2 -2.8 |
Females | Premating weeks 1 -10 | 1.3 -0.6 | 2.6 -1.2 | 6.5 -3.3 | |
Gestation week 1 | 0.7 | 1.4 | 3.6 | ||
Gestation week 2 | 0.7 | 1.4 | 3.6 | ||
Gestation week 3 | 0.5 | 0.9 | 2.3 | ||
Lactation week 1 | 1.0 | 2.1 | 4.8 | ||
Lactation week 2 | 1.7 | 3.4 | 8.5 | ||
Lactation week 3* | 2.1 | 4.4 | 10.9 |
* As pups started to eat on approximately post natal day 14, test substance intake in lactation week 3 is unrealistic.
Values are group means; during premating, n=7 cages/group/sex; during gestation and lactation, n=19 -27 female rats/group.
Table 2 Reproductive performance of female rats
Phytosterol esters (% of diet) | |||||
Parameter | Generation | 0 | 1.6 | 3.2 | 8.1 |
Mating index (%)1 | F0 | 100 | 100 | 100 | 100 |
F1 | 100 | 100 | 100 | 96 | |
Fertility index (%)2 | F0 | 100 | 96 | 86 | 93 |
F1 | 96 | 93 | 96 | 89 | |
Fecundity index (%)3 | F0 | 100 | 96 | 86 | 93 |
F1 | 96 | 93 | 96 | 93 | |
Gestation index (%)4 | F0 | 100 | 100 | 96 | 96 |
F1 | 100 | 100 | 96 | 100 | |
Precoital time (days)5 | F0 | 3.3 ± 0.65 | 3.7 ± 0.73 | 2.6 ± 0.23 | 2.4 ± 0.54 |
F1 | 2.4 ± 0.28 | 3.3 ± 0.51 | 2.6 ± 0.20 | 3.6 ± 0.63 | |
Gestation time (days)5 | F0 | 21.2 ± 0.11 | 21.4 ± 0.12 | 21.3 ± 0.14 | 21.4 ± 0.12 |
F1 | 21.2 ± 0.12 | 21.4 ± 0.11 | 21.4 ± 0.11 | 21.2 ± 0.11 | |
Post implantation loss/animal (%)5,6 | F0 | 15.31 ± 4.24 | 19.01 ± 3.83 | 19.33 ± 5.29 | 21.66 ± 5.18 |
F1 | 6.44 ± 1.43 | 13.05 ± 2.21 | 11.21 ± 3.78 | 10.81 ± 1.54 |
1 (no. of females mated/no. of females placed with males) X 100
2 (no. of females pregnant/no. of females placed with males) X 100
3 (no. of females pregnant/no. of females mated) X 100
4 (no. of females with live pups/no. of females pregnant) X 100
5 Values are means ± SEM; statistical test: Kruskal-Wallis + Mann-Whitney U test
6 Total post implantation loss = ((no. of implantation sites/no. of pups born alive)/no. of implantation sites) X 100
Table 3 Summary of offspring data
Phytosterol esters (% of diet) | |||||
Parameter | Generation | 0 | 1.6 | 3.2 | 8.1 |
Pups delivered (total)1 | F0 | 10.39 ± 0.37 | 10.26 ± 0.44 | 10.33 ± 0.48 | 9.68 ± 0.49 |
F1 | 10.56 ± 0.28 | 9.73 ± 0.44 | 9.96 ± 0.40 | 10.60 ± 0.27 | |
Live birth index (%)2,3 | F0 | 92 | 92 | 92 | 93 |
F1 | 100 | 98 | 99 | 98 | |
Pup mortality day 1 (%)2 | F0 | 8.2 | 8.3 | 8.5 | 7.0 |
F1 | 0 | 1.6 | 1.5 | 1.5 | |
Viability index day 4 (%)2,4 | F0 | 93.3 | 87.4* | 84.6** | 84.0** |
F1 | 98.9 | 97.2 | 95.8* | 89.7*** | |
Viability index day 21 (%)2,5 | F0 | 98 | 100 | 100 | 99 |
F1 | 99 | 99 | 99 | 100 | |
Dams with no deaths, day 216 | F0 | 20 | 17 | 13 | 14 |
F1 | 21 | 21 | 20 | 18 | |
Dams with 1 or more deaths, day 216 | F0 | 7 | 10 | 11 | 11 |
F1 | 6 | 5 | 7 | 7 | |
Whole litter losses2 | F0 | 3 | 3 | 2 | 5 |
F1 | 0 | 0 | 1 | 0 | |
Sex ratio day 1 (%)7 | F0 | 51 | 53 | 52 | 49 |
F1 | 53 | 50 | 48 | 60 |
1 Values are means ± SEM per litter, statistical test: Kruskal-Wallis + Mann-Whitney U test
2 Statistical test: Fisher's exact test (*P<0.05; **P<0.01; ***P<0.001)
3 (no. of pups born alive/no. of pups born) X 100
4 (no. of pups at day 4/no. of live pups at day 1) X 100
5 (no. of pups at day 21/no. of live pups at day 4) X 100
6 Litter data analysed by Kruskal-Wallis
7 % of male pups of total live pups at day 1
Applicant's summary and conclusion
- Conclusions:
- In a dietary two-generation reproductive toxicity study conducted using a protocol comparable with OECD 416 and in compliance with GLP (reliability 1) no adverse effects were reported for general systemic toxicity, or reproductive and developmental toxicity in any generation. The highest concentration tested was 8.1% (w/w) phytosterol ester in diet. This gave a NOAEL of 2500-9100 mg/kg bw/day phytosterol ester or 1540-5620 mg/kg bw/day phytosterol.
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