Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-881-1 | CAS number: 111-55-7
- 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:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 31 May - 05 Oct 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- adopted 29 Jul 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Government of India, Department of Science and Technology, New Delhi, India
- Limit test:
- no
Test material
- Reference substance name:
- Ethylene di(acetate)
- EC Number:
- 203-881-1
- EC Name:
- Ethylene di(acetate)
- Cas Number:
- 111-55-7
- Molecular formula:
- C6H10O4
- IUPAC Name:
- 2-(acetyloxy)ethyl acetate
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Expiration date of the batch: 20 Oct 2019
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 15 to 25 °C
- Solubility and stability of the test substance in the vehicle were confirmed by analytical methods
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- HanTac: WH
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Vivo Bio Tech Ltd., Medak District, Telangana, India
- Age at study initiation: 12 - 13 weeks
- Weight at study initiation: 275.04 - 347.30 g (males) and 173.29 - 209.05 g (females)
- Housing: Pre-mating: two rats of the same sex in sterilised standard polysulfone cages (size 425 x 266 x 185 mm) with a stainless steel top grill having facilities for pelleted food and water supply, steam sterilised clean corn cob as bedding
- Housing: Mating and post-mating: two rats (1 male, 1 female) in sterilised standard polysulfone cages (size 425 x 266 x 185 mm) with a stainless steel top grill having facilities for pelleted food and water supply. After confirming the presence of sperm in the vaginal smear or vaginal plugs, the mated pairs were separated. Males were housed with their former cage mates while females were housed individually in polysulfone cages. Sterilised nesting material was provided near-term.
- Diet: Teklad Certified (2014C) Global 14% Protein Rodent Maintainance Diet - Pellet, Envigo, Madison, Wisconsin, ad libitum
- Water: Deep bore-well water passed through an activated charcoal filter and exposed to UV rays in 'Aquagard' on-line water filter-cum-purifier (Eureka Forbes Limited, Mumbai, India), ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 57 - 67
- Air changes (per hr): 12.3 - 13.6
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 25 Jun 2018 To:13 Aug 2018
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared daily. Required quantities was weighed for each dose level separately into a beaker and a small volume of vehicle (corn oil) was added and stirred using a glass rod till a uniform suspension was obtained. The volume was made up to the mark using the vehicle to yield final concentrations of 20, 60 and 200 mg/mL. The suspensions were mixed well by stirring using a magnetic stirrer.
VEHICLE
- Justification for use and choice of vehicle: Based on a solubility test, the test item forms uniform suspension in corn oil. Hence, corn oil was used as vehicle for dose formulation preparations.
- Concentration in vehicle: 20, 60 and 200 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: Until there was evidence of sperm in the vagina smear or a vaginal plug. All females were successfully copulated within five days from the day of cohabitation.
- Proof of pregnancy: vaginal plug and/or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged: individually - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For homogeneity and test item concentration analysis, prepared formulation samples were sampled in duplicate sets on Day 1 of the treatment period and during the 2nd month (Day 32) of treatment and analysed. For each set, duplicate samples were drawn from the top, middle and bottom-layers of each preparation and in case of the control duplicate samples from the middle layer were drawn. The test item in the dose formulation was determined using Gas Chromatograph with Flame Ionisation Detection (FID). The test item was used as the analytical standard.
The results were considered acceptable, as the percent agreement of the analysed concentrations were in the range 85% to 115% of the claimed concentrations. Homogeneity of the dose formulation was considered acceptable as the % relative standard deviation from six replicates at each dose level were ≤ 10%. - Duration of treatment / exposure:
- Males: 43 days
Females: maximum period of 56 days (14 days pre-mating until lactation day 14 when parental females were sacrificed) - Frequency of treatment:
- daily, 7 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels were based on the results of a preliminary range-finding study, in which animals were orally exposed to 50, 200, 500 and 1000 mg/kg bw/day for 14 days. The test item did not cause any toxicological effect on general health at any dose tested in either sex.
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: prior to treatment on Day 1 and at weekly intervals thereafter during the treatment period
- In the detailed clinical examination the animals were observed for changes in skin, fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g. lacrimation, piloerection, pupil size, unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements and stereotypies (e.g. excessive grooming, repetitive circling or bizzare behavior like self-mutilation, walking backwards) were recorded.
BODY WEIGHT: Yes
- Time schedule for examinations: prior to treatment on Day 1 and at weekly intervals thereafter. Individual body weights of females were recorded in the same manner until cohabitation (till mating confirmation) with males.
FOOD CONSUMPTION: Yes
- Food consumption was calculated by using the food consumed at each interval per cage and dividing by the number of rats per cage and the number if days in the intervening period to determine the food consumption/rat/day. Food consumption was not measured during the cohabitation period. Food consumption of pregnant dams was recorded on GD 7, 14, 20 and on Days 4 and 13 of the lactation period.
WATER CONSUMPTION: No - Oestrous cyclicity (parental animals):
- Vaginal smear was examined and the stage of oestrous cycle was recorded daily for two weeks before start of the treatment to select females with regular 4-5 days cyclicity for the study. The vaginal smear was also examined daily from the beginning of the treatment period until evidence of mating to determine the Day 0 of pregnancy/treatment-related effects on mating or precoital time. The time interval (in days) from the diestrus of an oestrous cycle to the next diestrus was considered as the oestrous cycle length of an animal.
- Sperm parameters (parental animals):
- Tissues collected form all animals in the control and high dose groups were examined microscopically for histopathological changes, including the qualitative assessment of all stages of spermatogenesis and interstitital testicular cell structure in the testis.
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter (4/sex/litter as nearly as possible); excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring: number and sex of pups, stillbirths, live births, postnatal mortality/ cannibalised pups, presence of gross anomalies/malformations, weight gain, physical or behavioral abnormalities, ano-genital distance (AGD), presence of nipples/areolae in male pups
GROSS EXAMINATION OF DEAD PUPS: Yes, for external deformities; possible cause of death was determined for pups born or found dead.
HORMONE ANALYSIS: Blood samples were collected and serum was separated for the determination of total rodent thyroxin (T4) and rodent thyroid stimulating hormone (TSH) on Day 4 after birth. T4 and TSH were estimated by Enzyme Linked Immuno Sorbent Assay (ELISA). - Postmortem examinations (parental animals):
- SACRIFICE: Terminally sacrificed adult animals were fasted overnight (water allowed), weighed and exsanguinated under isoflurane anaesthesia.
- Male animals: All male animals were sacrificed on Day 44.
- Maternal animals: All female were sacrificed on Lactation Day 14. One dam was pre-terminally found dead on gestation Day 19.
GROSS NECROPSY: Yes
Gross necropsy consisted of external and internal examinations. External macroscopical examination paid attention to all organs listed below, as well as the external genitals which were examined for signs of altered development. The following organs were microscopically examined: adrenals, epididymides, ovaries with oviducts, stomach, thymus, thyroid with parathyroids, uterus with cervix, vagina, prostate, seminal vesicles and coagulating glands, testes, levator ani bulbocavernosus muscle complex, cowper’s glands, glans penis.
HISTOPATHOLOGY / ORGAN WEIGHTS: Yes
The following tissues were prepared for microscopic examination and weighed, respectively: adrenals, epididymides, ovaries with oviducts, stomach, thymus, thyroid with parathyroids, uterus with cervix, vagina, prostate, seminal vesicles and coagulating glands, testes, levator ani bulbocavernosus muscle complex, cowper’s glands, glans penis. Samples from all tissues were preserved in 10% neutral buffered formalin, except for the testes. - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at day 13 post-partum
- These animals were subjected to post-mortem detailed macroscopic examinations as follows:
GROSS NECROPSY: Yes
Gross necropsy consisted of external and internal examinations. External macroscopical examination paid attention to all organs listed below, as well as the external genitals which were examined for signs of altered development. The following organs were microscopically examined: adrenals, epididymides, ovaries with oviducts, stomach, thymus, thyroid with parathyroids, uterus with cervix, vagina, prostate, seminal vesicles and coagulating glands, testes, levator ani bulbocavernosus muscle complex, cowper’s glands, glans penis.
HISTOPATHOLOGY / ORGAN WEIGHTS: Yes
The following tissues were prepared for microscopic examination and weighed, respectively: adrenals, epididymides, ovaries with oviducts, stomach, thymus, thyroid with parathyroids, uterus with cervix, vagina, prostate, seminal vesicles and coagulating glands, testes, levator ani bulbocavernosus muscle complex, cowper’s glands, glans penis. Samples from all tissues were preserved in 10% neutral buffered formalin, except for the testes. - Statistics:
- Built-in statistical tests were used to analyse net body weight gain, food consumption, ano-genital ratio, oestrous cycle length, organ weight ratios, post implantations, pre-coital intervals, mean litte size, sex ratio and gestation length (days), mating, fertility and survival indices. Data was captured using ProvantisTM. Hormonal data was statistically analysed using SYSTAT Statistical package version 12.0. The following tests were applied:
- Levene’s test for homogeneity of variances
- ANOVA using log transformation for one-way analysis of variances (non-optimal/non-normal or heteroschedastic data was transformed prior to ANOVA)
- Dunnett’s t-test for comparison of means between treatment groups and control groups (overall treatment)
- F-test for statistical significance - Reproductive indices:
- - Male mating index [%] = Number of males with evidence of mating/Number of males cohabited x 100
- Male fertility index [%] = Number of males siring a litter/impregnated a female/Number of males cohabited x 100
- Female mating index [%] = Number of females mated/Number of females cohabited x 100
- Female fertility index [%] = Number of pregnant females/Number of females used for mating x 100
- Mean number of implantations/group = Total number of implantations/Total number of pregnant animals
- Post implantation loss [%] = (Number of implantations – Number of live pups)/Number of implantations x 100 - Offspring viability indices:
- - Mean litter size per group = Total number of pups born/Total number of littered animals
- Mean viable litter size = Number of viable pups/Number if females littered
- Live birth index [%] = Number of viable pups born (at first observation)/Total number of pups born (At first observation) x 100
- Day 4 survival index [%] = Number of viable pups on lactation day 4/Number of viable pups born x 100
- Sex ratio [%] = Number of male pups born/Total number of pups born x 100
- Ano-genital Distance Ratio [mm/g1/3] = Ano-genital distance/Cube root of body weight
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- control group: one dead female rat on gestation day 19
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/day: significantly higher absolute body weight gains in females during days 1-15
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- 100 mg/kg bw/day: significantly increased food consumption during days 1-8 in female rats
- 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:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive performance:
- no effects observed
Details on results (P0)
One female rat from the control group (Rv117) was found dead on gestation day 19.
BODY WEIGHT AND WEIGHT CHANGES:
The mean body weights and body weight gains were unaffected throughout the treatment period in males and two weeks pre-mating period in females at all the tested doses when compared to vehicle control group. The absolute body weight gains (Day 1-15) were significantly higher in females at 1000 mg/kg bw/day. This was considered toxicologically not significant, as there were no significant differences observed in weekly mean body weights and food consumption.
FOOD CONSUMPTIONS:
The food consumption was not altered throughout the treatment period when compared to the vehicle control. An incidence of statistically significant increase in the food consumption was observed during days 1-8 in the 100 mg/kg bw/day dose group females and it was not related to treatment.
ESTROUS CYCLE:
The calculated mean oestrous cycle length in treated groups was not significantly different from those of the vehicle control group.
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, non-treatment-related
- 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:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 1: Summary of detailed clinical examination, clinical signs and mortality
Observation Type: All Types From Day 1 (Start) to 44 (End) |
Male | Female | ||||||
0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 | |
mg/kg bwt/day | mg/kg bwt/day | |||||||
Normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Dead | 1 | 0 | 0 | 0 | ||||
Total litter loss | 0 | 0 | 1 | 1 | ||||
Not littered | 0 | 1 | 0 | 0 |
Table 2: Summary of body weight and body weight gains
Day(s) Relative to Start Date | Males | Females | ||||||||
0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 | |||
mg/kg bw/day | mg/kg bw/day | |||||||||
Body Weight (g) | 1 [a] | Mean | 308.72 | 306.35 | 305.3 | 306.54 | 194.16 | 193.28 | 193.83 | 194.39 |
SD | 22.61 | 19.07 | 18.62 | 18.75 | 9.09 | 10.6 | 10.9 | 9.99 | ||
N | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | ||
8 [a] | Mean | 320.57 | 319.68 | 316.24 | 318.3 | 194.76 | 198.37 | 199.22 | 200.97 | |
SD | 23.76 | 21.81 | 19.94 | 21.85 | 9.95 | 9.77 | 13.55 | 11.99 | ||
N | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | ||
15 [a] | Mean | 332.21 | 331.14 | 323.48 | 330.4 | 200.12 | 203.82 | 203.3 | 206.06 | |
SD | 25.87 | 22.91 | 25.32 | 24.6 | 11.21 | 9.43 | 14.96 | 13.48 | ||
N | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | ||
22 [a] | Mean | 338.67 | 339 | 331.85 | 336.39 | |||||
SD | 26.26 | 24.07 | 26.8 | 27.52 | ||||||
N | 10 | 10 | 10 | 10 | ||||||
29 [a] | Mean | 347.19 | 347.84 | 339.79 | 344.54 | |||||
SD | 29.72 | 24.62 | 29.13 | 29.91 | ||||||
N | 10 | 10 | 10 | 10 | ||||||
36 [a] | Mean | 356.25 | 356.68 | 351.77 | 350.89 | |||||
SD | 31.5 | 26.76 | 30.05 | 28.94 | ||||||
N | 10 | 10 | 10 | 10 | ||||||
43 [a] | Mean | 362.23 | 366.9 | 364.88 | 360.56 | |||||
SD | 29.12 | 28.81 | 30.62 | 29.93 | ||||||
N | 10 | 10 | 10 | 10 | ||||||
Absolute Weight Gain (g) | 1 → 43 [a] | Mean | 53.51 | 60.55 | 59.58 | 54.02 | 5.97 | 10.54 | 9.47 | 11.67* |
SD | 9.51 | 12.84 | 21.93 | 16.9 | 4.89 | 3.73 | 5.32 | 5.64 | ||
N | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
[a] ANOVA and Dunnett test (Log)
* p < 0.05
Table 3: Summary of food consumption (g/rat/day)
Day(s) Relative to Start Date | Males | Females | |||||||
0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 | ||
mg/kg bw/day | mg/kg bw/day | ||||||||
1 → 8 | Mean | 16.8 | 16.92 | 16.13 | 17.17 | 12.3 | 13.82* | 12.63 | 13.42 |
SD | 0.57 | 1.58 | 0.83 | 1.24 | 0.84 | 1.48 | 1.17 | 0.9 | |
N | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
8 → 15 | Mean | 15.67 | 16.07 | 14.82 | 16.43 | 11.94 | 12.7 | 12.52 | 12.68 |
SD | 0.56 | 1.72 | 1.27 | 1.25 | 0.74 | 1.02 | 1.24 | 0.95 | |
N | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
22 → 29 | Mean | 16 | 15.58 | 15.5 | 15.76 | ||||
SD | 0.24 | 0.88 | 0.66 | 0.93 | |||||
N | 10 | 10 | 10 | 10 | |||||
29 → 36 | Mean | 16.4 | 16.36 | 16.93 | 16.68 | ||||
SD | 0.47 | 1.56 | 1.09 | 0.87 | |||||
N | 10 | 10 | 10 | 10 | |||||
36 → 43 | Mean | 15.13 | 15.25 | 15.91 | 15.2 | ||||
SD | 0.57 | 1.64 | 1.05 | 0.89 | |||||
N | 10 | 10 | 10 | 10 |
ANOVA and Dunnett test (Log)
* p < 0.05
Table 4: Summary of oestrous cycle length prior to cohabitation period
Day(s) Relative to Start | Date | Females | ||||
0 | 100 | 300 | 1000 | |||
mg/kg bw/day | ||||||
Mean | 1 → 15 [a] | Mean | 4 | 4.3 | 4.2 | 4.6 |
Cycle days) | SD | 0 | 0.3 | 0.3 | 0.9 | |
N | 10 | 10 | 10 | 10 |
ANOVA and Dunnett test (Log)
Table 5: Summary of maternal body weights and body weight gain during gestation and lactation period
Day(s) Relative to Mating | Females | Day(s) Relative to Littering | Females | |||||||||
0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 | |||||
mg/kg bw/day | mg/kg bw/day | |||||||||||
Body weight (g) |
0 [a] | Mean | 202.26 | 205.16 | 204.37 | 208.04 | 0 [a] | Mean | 217.16 | 214.1 | 222.79 | 224.03 |
SD | 11.05 | 8.67 | 16.37 | 12.96 | SD | 15.27 | 10.09 | 13.48 | 22.52 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 10 | 10 | |||
7 [a] | Mean | 221.18 | 224.15 | 224.67 | 230.75 | 4 [a] | Mean | 223.05 | 225.2 | 233.29 | 231.78 | |
SD | 10.23 | 11.14 | 15.22 | 14.44 | SD | 15.61 | 9.61 | 14.17 | 20.16 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 10 | |||
14 [a] | Mean | 246.02 | 248.35 | 249.87 | 256.83 | 7 [a] | Mean | 231.92 | 232.98 | 235.73 | 240.83 | |
SD | 11.83 | 11.15 | 16.15 | 19.27 | SD | 18.34 | 12.78 | 21.01 | 18.68 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
20 [a] | Mean | 293.6 | 295.93 | 300.27 | 308.17 | 13 [a] | Mean | 236.55 | 235.35 | 242.55 | 250.98 | |
SD | 16.72 | 13.18 | 19.94 | 18.64 | SD | 18.62 | 13.05 | 14.53 | 23.01 | |||
N | 9 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
Absolute weight gain (g) |
0 → 7 [a] | Mean | 18.92 | 18.98 | 20.3 | 22.71 | 0 → 4 [a] | Mean | 5.89 | 11.1 | 11.3 | 7.75 |
SD | 4.24 | 3.76 | 3.3 | 4.1 | SD | 6.13 | 6.66 | 5.42 | 7.22 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 10 | |||
7 → 14 [a] | Mean | 24.84 | 24.2 | 25.2 | 26.07 | 4 → 7 [a] | Mean | 8.87 | 7.77 | 2.44 | 6.84 | |
SD | 3.16 | 2.87 | 3.08 | 6.35 | SD | 5.23 | 8.87 | 8.69 | 7.93 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
14 → 20 [a] | Mean | 48.18 | 47.58 | 50.41 | 51.34 | 7 → 13 [a] | Mean | 4.63 | 2.37 | 6.82 | 10.15 | |
SD | 5.42 | 3.46 | 6.84 | 5.89 | SD | 8.88 | 5.78 | 9.07 | 10.28 | |||
N | 9 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
0 → 20 [a] | Mean | 92.44 | 90.76 | 95.9 | 100.13 | 0 → 13 [a] | Mean | 19.39 | 21.25 | 20.56 | 23.58 | |
SD | 9.34 | 5.75 | 6.75 | 10.71 | SD | 8.31 | 10.21 | 6.7 | 9.99 | |||
N | 9 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 |
[a] ANOVA and Dunnett test (Log)
Table 6: Summary of maternal food consumption during gestation and lactation period
Day(s) Relative to Mating | Females | Day(s) Relative to Littering | Females | |||||||||
0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 | |||||
mg/kg bw/day | mg/kg bw/day | |||||||||||
Total Food Consumption (g) | 0 → 7 [a] | Mean | 97.97 | 103.17 | 99.19 | 106.3 | 0 → 4 [a] | Mean | 97.03 | 96.9 | 103.69 | 93.8 |
SD | 6.79 | 9.01 | 9.92 | 9.84 | SD | 26.92 | 8.83 | 18.58 | 18.75 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 10 | |||
7 → 14 [a] | Mean | 121.13 | 123.03 | 123.02 | 130.9 | 4 → 13 [a] | Mean | 337.72 | 337.35 | 335.7 | 343.46 | |
SD | 10.05 | 10.41 | 8.5 | 17.7 | SD | 39.91 | 34.21 | 35.43 | 36.59 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
14 → 20 [a] | Mean | 111.17 | 107.38 | 113.12 | 119.65 | 0 → 13 [a] | Mean | 434.76 | 434.25 | 439.38 | 439.86 | |
SD | 9.7 | 9.2 | 10.72 | 10.13 | SD | 64.32 | 31.58 | 52.13 | 49.97 | |||
N | 9 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
0 → 20 [a] | Mean | 331.5 | 333.58 | 335.33 | 356.85 | |||||||
SD | 21.5 | 22.55 | 24.48 | 31.55 | ||||||||
N | 9 | 9 | 10 | 10 | ||||||||
Food Mean Consumption (g/day) | 0 → 7 [a] | Mean | 14 | 14.74 | 14.17 | 15.19 | 0 → 4 [a] | Mean | 24.26 | 24.23 | 25.92 | 23.45 |
SD | 0.97 | 1.29 | 1.42 | 1.41 | SD | 6.73 | 2.21 | 4.64 | 4.69 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 10 | |||
7 → 14 [a] | Mean | 17.3 | 17.58 | 17.57 | 18.7 | 4 → 13 [a] | Mean | 37.52 | 37.48 | 37.3 | 38.16 | |
SD | 1.44 | 1.49 | 1.21 | 2.53 | SD | 4.43 | 3.8 | 3.94 | 4.07 | |||
N | 10 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
14 → 20 [a] | Mean | 18.53 | 17.9 | 18.85 | 19.94 | 0 → 13 [a] | Mean | 33.44 | 33.4 | 33.8 | 33.84 | |
SD | 1.62 | 1.53 | 1.79 | 1.69 | SD | 4.95 | 2.43 | 4.01 | 3.84 | |||
N | 9 | 9 | 10 | 10 | N | 9 | 9 | 9 | 9 | |||
0 → 20 [a] | Mean | 16.57 | 16.68 | 16.77 | 17.84 | |||||||
SD | 1.08 | 1.13 | 1.22 | 1.58 | ||||||||
N | 9 | 9 | 10 | 10 |
[a] ANOVA and Dunnett test (Log)
Table 7: Summary of mean pup body weights, ano-genital distance (AGD)m Ano-genital ratio (AGR) and ano-genital index (AGI)
Day(s) Relative to Littering | Females | |||||
0 |
100 |
300 |
1000 |
|||
mg/kg bw/day | ||||||
Litter Mean |
0 [a] |
Mean |
5.74 |
5.43 |
5.98 |
5.83 |
SD | 0.58 | 0.52 | 0.59 | 0.81 | ||
N | 9 | 9 | 9 | 10 | ||
4 [a] |
Mean |
8.67 |
8.01 |
8.74 |
8.81 |
|
SD |
1.39 |
0.89 |
1.21 |
1.79 |
||
N |
9 |
9 |
9 |
9 |
||
7 [a] | Mean | 12.38 | 11.84 | 12.53 | 12.84 | |
SD | 1.46 | 1.07 | 1.5 | 2.26 | ||
N | 9 | 9 | 9 | 9 | ||
13 [a] | Mean | 20.62 | 20.38 | 20.75 | 21.71 | |
SD | 1.98 | 1.35 | 2.25 | 2.7 | ||
N | 9 | 9 | 9 | 9 | ||
Litter Mean Pup BW - F |
0 [a] | Mean | 5.68 | 5.25 | 5.68 | 5.63 |
SD | 0.57 | 0.5 | 0.5 | 0.78 | ||
N | 9 | 9 | 9 | 10 | ||
4 [a] | Mean | 8.55 | 7.86 | 8.28 | 8.76 | |
SD | 1.09 | 1.04 | 0.96 | 1.81 | ||
N | 9 | 9 | 9 | 9 | ||
7 [a] | Mean | 12.26 | 11.43 | 11.99 | 12.59 | |
SD | 1.41 | 1.31 | 1.34 | 2.06 | ||
N | 9 | 9 | 9 | 9 | ||
13 [a] | Mean | 20.47 | 19.7 | 20.01 | 21.4 | |
SD |
1.74 |
0.92 |
2.04 |
2.7 |
||
N | 9 | 9 | 9 | 9 | ||
Litter Mean Pup BW |
0 [a] | Mean | 5.69 | 5.33 | 5.85 | 5.72 |
SD | 0.55 | 0.5 | 0.55 | 0.77 | ||
N | 9 | 9 | 9 | 10 | ||
4 [a] | Mean | 8.6 | 7.91 | 8.54 | 8.77 | |
SD | 1.22 | 0.94 | 1.12 | 1.8 | ||
N | 9 | 9 | 9 | 9 | ||
7 [a] |
Mean |
12.32 |
11.61 |
12.3 |
12.68 |
|
SD |
1.39 |
1.13 |
1.46 |
2.08 |
||
N | 9 | 9 | 9 | 9 | ||
13 [a] |
Mean |
20.55 |
20.02 |
20.41 |
21.53 |
|
SD | 1.8 | 0.97 | 2.14 | 2.62 | ||
N | 9 | 9 | 9 | 9 | ||
Mean of pup AGD males |
0 [a] | Mean | 3.7 | 3.7 | 3.69 | 3.69 |
SD |
0.04 |
0.07 |
0.06 |
0.14 |
||
N | 9 | 9 | 9 | 10 | ||
Mean of pup AGD females |
0 [a] | Mean | 1.69 | 1.67 | 1.66 | 1.65 |
SD | 0.04 | 0.05 | 0.06 | 0.06 | ||
N | 9 | 9 | 9 | 10 | ||
Mean of pup |
0 [a] |
Mean |
2.07 |
2.11 |
2.04 |
2.05 |
SD | 0.05 | 0.04 | 0.05 | 0.04 | ||
N | 9 | 9 | 9 | 10 | ||
Mean of pup AGR females |
0 [a] | Mean | 0.95 | 0.96 | 0.93 | 0.93 |
SD | 0.04 | 0.03 | 0.02 | 0.03 | ||
N |
9 |
9 |
9 |
10 |
||
Mean of pup AGI males |
0 [a] | Mean | 2.1 | 2.1 | 2 | 2.1 |
SD | 0.1 | 0 | 0 | 0 | ||
N | 9 | 9 | 9 | 10 | ||
Mean of pup |
0 [a] |
Mean |
0.9 |
1 |
0.9 |
0.9 |
SD | 0 | 0 | 0 | 0 | ||
N | 9 | 9 | 9 | 10 |
[a] ANOVA and Dunnett test (Log)
Table 8: Summary of fertility data
Day(s) Relative to Mating | Males and females | |||||
0 | 100 | 300 | 1000 | |||
mg/kg bw/day | ||||||
Paired Males | - | N | 10 | 10 | 10 | 10 |
Paired Females | - | N | 10 | 10 | 10 | 10 |
Mated | - | N+ve | 10 | 10 | 10 | 10 |
Fertile Male | - | N+ve | 10 | 9 | 10 | 10 |
Fertile Female | - | N+ve | 10 | 9 | 10 | 10 |
M Mating Index | - [a] | % | 100 | 100 | 100 | 100 |
F Mating Index | - [a] | % | 100 | 100 | 100 | 100 |
Pregnant | - | N+ve | 10 | 9 | 10 | 10 |
Littered | - | N+ve | 9 | 9 | 10 | 10 |
Pre-coital Interval (f) (days) | - [a] | Mean SD N | 2.2 | 2 | 2.1 | 2.3 |
1.2 | 1.2 | 0.9 | 1.1 | |||
10 | 10 | 10 | 10 | |||
F Fertility Index | - [a] | % | 100 | 90 | 100 | 100 |
M Impregnated Female | - [a] | % | 100 | 90 | 100 | 100 |
[a] ANOVA and Dunnett test (Log)
M- male
F- female
Table 9: Summary of litter data
Day(s) Relative to Littering | Females | |||||
0 | 100 | 300 | 1000 | |||
mg/kg bw/day | ||||||
Littered | - | N+ve | 9 | 9 | 10 | 10 |
Gestation Length (days) |
- [a] | Mean | 22.4 | 22.1 | 22.5 | 22.5 |
SD | 0.5 | 0.3 | 0.7 | 0.5 | ||
N | 9 | 9 | 10 | 10 | ||
Total No of Pups Born Day 0 | - | Mean | 11 | 12 | 10 | 11 |
SD | 2 | 2 | 4 | 2 | ||
N | 9 | 9 | 10 | 10 | ||
Sum | 99 | 108 | 104 | 111 | ||
Dead/Canibalism | LD 0 | Sum | 3 | . | 2 | 8 |
Live Male Pups | LD 0 | Sum | 41 | 53 | 53 | 48 |
Live Female Pups | LD 0 | Sum | 55 | 55 | 49 | 55 |
Live Pups Day 0 | - [a] | Mean | 10.7 | 12 | 11.3 | 10.3 |
SD | 1.3 | 2 | 2.2 | 2.1 | ||
N | 9 | 9 | 9 | 10 | ||
Sum | 96 | 108 | 102 | 103 | ||
Live Birth Index (%) Day 0 | - [a1] | Mean | 97.3 | 100 | 90 | 94.7 |
SD | 5.4 | 0 | 31.6 | 16.9 | ||
N | 9 | 9 | 10 | 10 | ||
Sex Ratio Day 0 | - [a1] | Mean | 42.5 | 49.2 | 56.7 | 44.1 |
Dead/Cannibalism | LD 1 | Sum | 1 | 1 | . | 2 |
Live Pups Day 1 | - | Mean | 10.6 | 11.9 | 11.3 | 10.1 |
SD | 1.1 | 1.9 | 2.2 | 2.5 | ||
N | 9 | 9 | 9 | 10 | ||
Sum | 95 | 107 | 102 | 101 | ||
Dead/Cannibalism | LD 2-4 | Sum | 4 | 1 | . | 12 |
Live Pups Day 4 | - [a] | Mean | 10.1 | 11.8 | 11.3 | 9.9 |
SD | 1.1 | 1.8 | 2.2 | 2.6 | ||
N | 9 | 9 | 9 | 9 | ||
Sum | 91 | 106 | 102 | 89 | ||
No. of Pups Culled D4 | - | Sum | 19 | 34 | 30 | 21 |
No.of Live Pup Post Cu | ll - | Sum | 72 | 72 | 72 | 68 |
Survival Index on LD4 | - [a] | Mean | 95.6 | 98.4 | 100 | 86.2 |
SD | 10.3 | 3.1 | 0 | 31.6 | ||
N | 9 | 9 | 9 | 10 | ||
Dead/Cannibalism | LD 5-7 | Sum | 1 | 0 | 0 | 0 |
Live Pups Day 7 | - [a1] | Mean | 7.9 | 8 | 8 | 7.6 |
SD | 0.3 | 0 | 0 | 1 | ||
N | 9 | 9 | 9 | 9 | ||
Sum | 71 | 72 | 72 | 68 | ||
Survival Index on LD7 | - [a] | Mean | 98.6 | 100 | 100 | 100 |
SD | 4.2 | 0 | 0 | 0 | ||
N | 9 | 9 | 9 | 9 | ||
Dead/Cannibalism | LD 8-13 | Sum | 0 | 0 | 0 | 0 |
Live Pups Day 13 | - | Mean | 7.9 | 8 | 8 | 7.6 |
SD | 0.3 | 0 | 0 | 1 | ||
N | 9 | 9 | 9 | 9 | ||
Sum | 71 | 72 | 72 | 68 | ||
No. Of Implantation | - [a1] | Mean | 12.6 | 13 | 12.4 | 12.9 |
SD | 1.3 | 1.7 | 2.9 | 1.7 | ||
N | 10 | 9 | 10 | 10 | ||
Sum | 126 | 117 | 124 | 129 | ||
Post-implantation Loss (%) | - [p] | Mean | 14.62 | 7.86 | 22.56 | 18.61 |
SD | 10.85 | 7.92 | 27.75 | 19.33 | ||
N | 9 | 9 | 10 | 10 |
[a] - Anova & Dunnett(Arc SineSQRT)
[a1] - Anova & Dunnett(Log)
[p] - T-Test(Arc SineSQRT): [G1vsG2, G1vsG3, G1vsG4]
Applicant's summary and conclusion
- Conclusions:
- The test item had no effect on reproductive performance.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.