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EC number: 248-595-8 | CAS number: 27668-52-6
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Developmental Toxicity Study of Quaternary Silsesquioxane in rats
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Details on test animals and env. conditions
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Portage, MI).
- Age at study initiation: 13 weeks
- Weight at study initiation: 206 to 275 g at gestation day 0
- Fasting period before study: No data available
- Housing: Animal were housed individually, except during mating, in suspended stainless steel wire mesh cages from receipt until sacrifice.
- Use of restrainers for preventing ingestion (if dermal): No data available
- Diet (e.g. ad libitum): basal laboratory diet of Certified Rodent Chow 5002 (Ralston Purina Co., St. Louis, MO), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 -20°C
- Humidity (%):Relative humidity: 30-70%
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12 hrs
IN-LIFE DATES: From: To: No data available - Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- corn oil
- Details on exposure:
- Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: Quat-Silsesquioxane was suspended fresh daily in corn oil
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): corn oil.
- Concentration in vehicle: 0, 100, 300, and 1000 mg/kg/day
- Amount of vehicle (if gavage): 10 ml/kg.
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- - M/F ratio per cage:1:1
- Length of cohabitation:No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:Copulatory plug referred to as 0 of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.:No data available
- Further matings after two unsuccessful attempts: No data available
- After successful mating each pregnant female was caged (how):stainless steel wire mesh cages: Individually
- Any other deviations from standard protocol:No data available - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 10 days
- Frequency of treatment:
- Daily from gestation days 6 to 15
- Details on study schedule:
- No data available
- Remarks:
- Doses / Concentrations:
0, 100, 300 and 1000 mg/kg/day
Basis:
other: Dosage levels were selected from the results obtained in a range-finding developmental toxicity study - No. of animals per sex per dose:
- 25 rats per doses
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dosage levels were selected from the results obtained in a range-finding developmental toxicity study. In that study neither maternalnor developmental toxicity was seen at dosage levels of up to 1000 mg/kg/day.
- Rationale for animal assignment (if not random): Mated females were assigned consecutively, in the order the mating was detected
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups:No data available
- Section schedule rationale (if not random):No data available - Positive control:
- No data available
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked in table [No.?] were included. For changes in appearance, behavior and mortality.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: daily on Gestation Days 0,6,9, 12, 16, and 20.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):Yes
- 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: No data available
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
other:
organ weight: liver and gravid uterine weight was recorded - Oestrous cyclicity (parental animals):
- Nongravid Uteri were examined for Corpora lutea, Total implantation and Postimplantation loss.
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- viable fetuses, crown-rump length, fetal body weight and sex ratio were examined.
- Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: No data available
- Maternal animals: Yes, gross pathology were examined. - Postmortem examinations (offspring):
- Postmortem examinations (offspring)
SACRIFICE: Yes
GROSS NECROPSY: Yes
HISTOPATHOLOGY: Yes
One-half of the fetuses were examined for soft tissue and remaining half for subsequent skeletal examination. - Statistics:
- 1)Mean maternal body weights and liver weights, maternal feed consumption, numbers of corpora lutea, total implantations, live fetuses, gravid uterine weight, and mean fetal body weights were compared by one-way analysis of variance (ANOVA), Bartlett's test for homogeneity of variance, and the appropriate test for equal and unequal variance (Steel and Torrie, 1960) using Dunnett's multiple comparison.
2) The proportions of resorbed and dead fetuses and postimplantation losses were compared by the Mann-Whitney t/test.
3) Male to female fetal sex ratios and the proportions of litters with malformations and developmental variations were compared using the x1 test criterion with Yate's correction for 2 X 2 contingency tables and/or
Fisher's exact probability test. - Reproductive indices:
- Fertility and gestation were examined.
- Offspring viability indices:
- yes, viable fetuses were examined.
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- not specified
- Other effects:
- not specified
- Description (incidence and severity):
- Test substance intake: No data available
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No effect on survival, Clinical signs, Body weight, Organ weight and reproductive performance
- Clinical signs:
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effect on Viability , body weight, gross pathology and histopathology
- Reproductive effects observed:
- not specified
- Conclusions:
- NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawleyd female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
- Executive summary:
In a developmental toxicity study, Sprague-Dawley female rats were treated with Quat-Silsesquioxane in the concentration of 0, 100, 300, or 1000 mg/kg/day orally by gavage in corn oil.No maternal mortality and clinical signs or behavioral changes were observed in treated female rats as compared to control. No effect on body weight and feed consumption changes were observed in treated female rats as compared to control. Similarly, no effect on reproductive parameters such as number of corpora lutea, number of live fetuses per litter, litter size, mean fetal body weight, or mean crown-rump length was observed in treated rats. Ratio of male and female pups at the 1000 mg/ kg/day dose level was significantly different from the control group but was not considered treatment related. Slight but significant increase in relative liver weight of treated female rats was observed as compared to control. In addition, No effect on viability, fetal body weight and external malformations were observed in treated fetuses as compared to control. One fetus with bent limb bones, two fetuses from different mothers with microphthalmia and two other fetuses with omphalocele were observed at 1000 mg/kg/day and single fetus with multiple malformations were observed at 300 mg/kg/day in treated fetuses as compared to control. The incidence of developmental variations in the treated litters was not significantly increased over the control incidence. They occurred in low frequency and were distributed randomly across the Quat-Silsesquioxane treated and control groups. Therefore,NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawley female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
Reference
Clinical signs- No clinical signs or behavioral changes were observed in treated female rats as compared to control.
Body weights – No body weight changes were observed in treated femlae rats as compared to contorl.
Feed consumption - No feed consumption changes were observed in treated female rats as compared to control.
Reproductive funtion: estrous cycle:
No adverse effects on mean number of corpora lutea, number of live fetuses per litter, litter size, mean fetal body weight, or mean crown-rump length.
Reproductive performance:
Ratio of male and female pups at the 1000 mg/ kg/day dose level was significantly different from the control group but was not considered treatment related.
Organ weight - Slight but significant increase in relative liver weight of treated female rats was observed as compared to control.
Body weight: No significant effect were observed on fetal body weight as compared to control.
Gross pathology :No significant external malformations were observed in treated fetuses as compared to control.
Histopathology :
When treated with 1000 mg/kg bw, One fetus with bent limb bones, Two fetuses from different mothers with microphthalmia and two other fetuses with omphalocele were observed in treated fetuses as compared to control.
When treated with 300 mg/kg bw, single fetus with multiple malformations were observed in treated fetuses as compared to control.
The incidence of developmental variations in the treated litters was not significantly increased over the control incidence. They occurred in low frequency and were distributed randomly across the Quat-Silsesquioxane treated and control groups.
TABLE 1
Summary of Maternal Body Weight Gain, Food Consumption, and Liver Weights
|
Dose levels (mg/kg/day) |
||||
Gestation day |
0 |
100 |
300 |
1000 |
|
|
Mean body weight change (g) |
||||
0-6 |
26 ± 7a |
25 ±7 |
27 ±7 |
29 ±8 |
|
6-9 |
3 ± 8 |
3 ± 8 |
7±7 |
6 ± 8 |
|
9-12 |
16 ± 10 |
19 ±6 |
15 ± 4 |
15 ± 9 |
|
12-16 |
27 + 7 |
26 ± 12 |
22 ± 8 |
22 ± 11 |
|
16-20 |
59 ± 11 |
61 ± 17 |
62 ± 13 |
60 ± 15 |
|
0-20 |
131 ± 19 |
133 ±25 |
132 ± 19 |
132 ±25 |
|
0-20 adjustedb |
61 + 13 |
62 ± 14 |
62+13 |
66 ± 13 |
|
Mean food consumption (g/dam/day) |
|||||
0-6 |
21.5 + 2 |
21.5 ±2 |
22.3 ±2 |
22.0 ± 4 |
|
6-9 |
17.8 ± 4 |
15.2 ±3* |
17.9 ± 3 |
19.9 ± 8 |
|
9-12 |
17.9 ± 2 |
17.9 ± 2 |
19.9 ±3* |
21.2 ±8 |
|
12-16 |
19.8 ± 2 |
21.1 ±5 |
20.4 ± 3 |
20.2 ±4 |
|
16-20 |
27.3 ± 2 |
27.4 ±3 |
26.2 ±6 |
28.0 ±2 |
|
0-20 |
21.3+1 |
21.2 ± 2 |
21.7 ± 2 |
22.5 ± 3 |
|
Mean maternal liver weight(20 days of gestation) |
|||||
Absolute (g) |
15.4 + 2.9 |
15.3 ±2.9 |
16.1 ±2.6 |
16.5 ±2.5 |
|
Relative (%) |
4.4 ± 0.4 |
4.4 ± 0.3 |
4.5 ±0.3 |
4.6 ± 0.2* |
|
aMean ± SD.
bDam body weight minus the uterus and its contents.
* Significantly different from controls; ANOVA, Welch Test, P < 0.05
TABLE 2
Summary of Observations at Time of Cesarean Sections
|
Dose levels (mg/kg/day) |
|||
|
0 |
100 |
300 |
1000 |
Animals examined at cesarean sections |
25 |
25 |
25 |
25 |
Nongravid |
7 |
7 |
5 |
4 |
Gravid |
18 |
18 |
20 |
21 |
Dams with resorptions only |
0 |
0 |
0 |
0 |
Dams with viable fetuses |
18 |
18 |
20 |
21 |
Viable fetuses/dama |
13.3 ±2.7 |
13.3 ± 3.3 |
13.2 ± 4.2 |
12.4 ± 4.0 |
Postimplantation loss/dama |
1.1 ±0.8 |
0.6 ± 0.61 |
1 5 ± 2.31 |
0.8 + 0.8 |
Total implantation/dama |
14.4 ±2.5 |
13.9 ± 3.5 |
14.7 ± 3.4 |
13.2 ± 4.4 |
Corpora lutea/dama |
17.8 ±3.3 |
15.8 ± 2.6 |
17.7 ± 2.9 |
16.2 ± 3.2 |
Mean crown-rump length (cm) |
3.5 ±0.1 |
3.5 ± 0.2 |
3.5 ± 0 1 |
3.5 ± 0 1 |
Group mean uterine weights (g) |
70.1 ±14.1 |
71.3 ±17.7 |
70.3 ±21.2 |
66.5 ± 18.2 |
Group mean preimplantation loss (%) |
18.8 |
12.0 |
17.2 |
18.2 |
Group mean postimplantation loss (%) |
7.7 |
4.4 |
9.9 |
6.1 |
Mean fetal body weight (g) |
3.4 ±0.2 |
3.5 ± 0.5 |
3.4 ± 0.2 |
3.4 + 0.3 |
Fetal sex ratio—m:f (%) |
44:56 |
49:51 |
50:50 |
55:45* |
aMean ± SD.
* Significantly different; x2. P * 0.05.
TABLE 3
Summary of the Incidence of Fetal Malformations*
|
Dose levels (mg/kg/day) |
|||
|
No. examined |
|||
Litters |
18 |
18 |
20 |
21 |
Fetuses externally |
240 |
238 |
263 |
260 |
Fetuses viscerally |
119 |
118 |
132 |
129 |
Fetuses skeletally |
121 |
121 |
132 |
132 |
|
No.of fetuses (No. Of litters) affected |
|||
Malformations observed |
|
|
|
|
Anophthalmia |
1 (1) |
|
|
|
Microphthalmia |
|
|
|
2(2) |
Gastroschisis |
|
|
1(1) |
|
Omphalocele |
|
|
|
2(2) |
Tail agenesis |
|
|
1(1) |
|
Tarsal flexure |
|
|
1(1) |
|
Edema |
|
|
1(1) |
|
Malformed skull bones |
|
|
1(1) |
|
Bent clavicle |
|
|
1(1) |
|
Bent scapula |
|
|
1(1) |
|
Amelia |
|
|
1(1) |
|
Micromelia |
|
|
1(1) |
|
Bent limb bones |
1(1) |
|
|
1(1) |
Vertebral agenesis |
|
|
1(1) |
|
Pelvic malformation |
|
|
1(1) |
|
Total fetuses (litters) with malformations |
2(2) |
0(0) |
1(1) |
5(4) |
* No statistical significance was observed.
TABLE 4
Summary of the Incidence of Fetal Variations*
|
Summary of the Incidence of Fetal Variations* |
|||
|
Dose levels (mg/kg/day) |
|||
|
0 |
100 |
300 |
1000 |
|
No. examined |
|||
Litters |
18 |
18 |
20 |
21 |
Fetuses externally |
240 |
238 |
263 |
260 |
Fetuses viscerally |
119 |
118 |
132 |
129 |
Fetuses skeletally |
121 |
121 |
132 |
132 |
|
No.of fetuses (No. Of litters) affected |
|||
Developmental variations observed |
|
|
|
|
Renal papillae not developed |
|
1(1) |
1(1) |
|
Distended ureter |
|
1(1) |
1(1) |
|
Skull reduced in ossification |
2(1) |
3(2) |
2(2) |
|
Hyoid unossified |
1(1) |
|
1(1) |
1(1) |
25 presacral vertebrae |
|
|
1(1) |
2(2) |
Greater than 13 pairs of full ribs |
|
|
2(2) |
|
14th rudimentary rib(s) |
6(3) |
7(4) |
12(5) |
6(5) |
Bent ribs |
|
1(1) |
|
2(1) |
7th cervical rib |
3(3) |
|
2(2) |
|
Vertebrae reduced in ossification |
1(1) |
|
1(1) |
|
Misaligned sternebra(e) |
8(6) |
6(5) |
8(6) |
4(3) |
Sternebra 5 and/or 6 unossified |
3(5) |
7(6) |
4(4) |
8(6) |
Other sternebra(e) unossified |
1(1) |
|
1(1) |
1(1) |
Ischia reduced in ossification |
1(1) |
|
|
2(1) |
Total fetuses (litters) with developmental variations |
22(12) |
24(11) |
30(14) |
22(12) |
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from peer-reviewed journal
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity:
Data available for target 1-Octadecanaminium- N,N-dimethyl-N-{3- (trimethoxysilyl)propyl}- chloride (CAS no 27668-52-6) for reproductive toxicity are summarized as below
In a study conducted by Siddiquiet al(1993),reproductive toxicity was evaluated in Sprague-Dawley female rats by using Quat-Silsesquioxane in the concentration of 0, 100, 300, or 1000 mg/kg/day orally by gavage in corn oil.No maternal mortality and clinical signs or behavioral changes were observed in treated female rats as compared to control. No effect on body weight and feed consumption changes were observed in treated female rats as compared to control. Similarly, no effect on reproductive parameters such as number of corpora lutea, number of live fetuses per litter, litter size, mean fetal body weight, or mean crown-rump length was observed in treated rats. Ratio of male and female pups at the 1000 mg/ kg/day dose level was significantly different from the control group but was not considered treatment related. Slight but significant increase in relative liver weight of treated female rats was observed as compared to control. In addition, No effect on viability, fetal body weight and external malformations were observed in treated fetuses as compared to control. One fetus with bent limb bones, two fetuses from different mothers with microphthalmia and two other fetuses with omphalocele were observed at 1000 mg/kg/day and single fetus with multiple malformations were observed at 300 mg/kg/day in treated fetuses as compared to control. The incidence of developmental variations in the treated litters was not significantly increased over the control incidence. They occurred in low frequency and were distributed randomly across the Quat-Silsesquioxane treated and control groups. Therefore,NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawley female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
In a study conducted byDupont Chem Co (1992),teratogenicity was evaluated in Albinofemale rats by using Dow Corninc @Q9-5700 in the concentration of 0, 100, 300 and 1000 mg/kg orally. 1 nongravid rats died at 1000 mg/kg and 1 pregnant rats died at 100 mg/kg as compared to control. No untoward behavioral reactions were observed in treated female rats as compared to control.Similarly,Noeffect on gestation andgross pathological changes were observed in treated female rat as compared to control. In addition, No effect on fetuses Body weight were observed as compared to control. No external abnormalities and skeletal and internal developmental effect were observed in treated fetuses as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg for P and F1 generation when Albinofemale rats were treated with Dow Corninc @Q9-5700 orally from gestation days 6 through 15.
Thus, based on the above available data for targetQuat-Silsesquioxane(CAS no 27668-52-6) is likely to be non hazardous as reproductive toxicant.
Short description of key information:
Quat-Silsesquioxane (CAS no 27668-52-6) is likely to be non hazardous as reproductive toxicant.
Justification for selection of Effect on fertility via oral route:
NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawley female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
Effects on developmental toxicity
Description of key information
Quat-Silsesquioxane (CAS no 27668-52-6) is likely to be non hazardous as developmental toxicant.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from peer reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- The developmental toxicity of an antimicrobial organosilicon quaternary ammonium chloride (Quaternary Silsesquioxane) was evaluated in rats.
Study was conducted according to The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) - GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
-Sex: Female
- Source: Charles River Breeding Laboratories, Inc. (Portage, MI).
- Age at study initiation: 13 weeks
- Weight at study initiation: 206 to 275 g at gestation day 0
- Fasting period before study: No data available
- Housing: Animal were housed individually, except during mating, in suspended stainless steel wire mesh cages from receipt until sacrifice.
- Use of restrainers for preventing ingestion (if dermal): No data available
- Diet (e.g. ad libitum): basal laboratory diet of Certified Rodent Chow 5002 (Ralston Purina Co., St. Louis, MO), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 -20°C
- Humidity (%):Relative humidity: 30-70%
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12 hrs
IN-LIFE DATES: From: To: No data available - Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- corn oil
- Details on exposure:
- Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: Quat-Silsesquioxane was suspended fresh daily in corn oil
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): corn oil.
- Concentration in vehicle: 0, 100, 300, and 1000 mg/kg/day
- Amount of vehicle (if gavage): 10 ml/kg.
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Proof of pregnancy: Copulatory plug was designated Day 0 of gestation - Duration of treatment / exposure:
- 10 days
- Frequency of treatment:
- Single daily dose
- Duration of test:
- 20 days of gestation
- Remarks:
- Doses / Concentrations:
0, 100, 300, and 1000 mg/kg/day
Basis:
no data - No. of animals per sex per dose:
- Total: 100
0 mg/kg/day: 25 female
100 mg/kg/day: 25 female
300 mg/kg/day: 25 female
10000 mg/kg/day: 25 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dosage levels were selected from the results obtained in a range-finding developmental toxicity study. In that study neither maternalnor developmental toxicity was seen at dosage levels of up to 1000 mg/kg/day.
- Rationale for animal assignment (if not random): Mated females were assigned consecutively, in the order the mating was detected
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups:No data available
- Section schedule rationale (if not random):No data available - Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked in table [No.?] were included. For changes in appearance, behavior and mortality.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: daily on Gestation Days 0,6,9, 12, 16, and 20.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):Yes
- 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: No data available
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
other:
organ weight: liver and gravid uterine weight was recorded - Ovaries and uterine content:
- Nongravid Uteri were examined for Corpora lutea, Total implantation and Postimplantation loss.
- Fetal examinations:
- viable fetuses, crown-rump length, fetal body weight and sex ratio, gross pathology and histopathology were examined.
- Statistics:
- Mean maternal body weights and liver weights, maternal feed consumption, numbers of corpora lutea, total implantations,live fetuses, gravid uterine weight, and mean fetal body weights were compared by one-way analysis of variance (ANOVA), Bartlett's test for homogeneity of variance, and the appropriate t test for equal and unequal variance (Steel and Torrie, 1960) using Dunnett's multiple comparison(Dunnett, 1964). The proportions of resorbed and dead fetuses and postimplantation losses were compared by the Mann-Whitney t/test (Siegel,1956). Male to female fetal sex ratios and the proportions of litters with malformations and developmental variations were compared using the x1 test criterion with Yate's correction for 2 X 2 contingency tables and/or
Fisher's exact probability test (Siegel, 1956; Weil, 1970). All statistical analyses compared the mean values of the treated groups with those of the
control, with the levels of significance at p < 0.05 and p < 0.01. - Indices:
- Viability, Fertility and gestation were examined
- Historical control data:
- No data available
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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):
- no effects observed
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Mortality – No effect on survival of treated female rats were observed as compared to control.
Clinical signs- No clinical signs or behavioral changes were observed in treated female rats as compared to control.
Body weights – No body weight changes were observed in treated female rats as compared to control.
Feed consumption - No feed consumption changes were observed in treated female rats as compared to control.
Organ weight - Slight but significant increase in relative liver weight of treated female rats was observed as compared to control. - Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- Reproductive function: estrous cycle:
No adverse effects on mean number of corpora lutea, number of live fetuses per litter, litter size, mean fetal body weight, or mean crown-rump length.
Reproductive performance:
Ratio of male and female pups at the 1000 mg/ kg/day dose level was significantly different from the control group but was not considered treatment related. - Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Abnormalities:
- not specified
- Localisation:
- not specified
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- No developmental parameter such as viability, fetal body weight and external malformations were observed in treated fetuses as compared to control. One fetus with bent limb bones, two fetuses from different mothers with microphthalmia and two other fetuses with omphalocele were observed at 1000 mg/kg/day and single fetus with multiple malformations were observed at 300 mg/kg/day in treated fetuses as compared to control. The incidence of developmental variations in the treated litters was not significantly increased over the control incidence.
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- changes in sex ratio
- fetal/pup body weight changes
- external malformations
- Abnormalities:
- not specified
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Developmental effects observed:
- not specified
- Conclusions:
- NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawleyd female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
- Executive summary:
In a developmental toxicity reproductive toxicity was evaluated in Sprague-Dawley female rats by using Quat-Silsesquioxane in the concentration of 0, 100, 300, or 1000 mg/kg/day orally by gavage in corn oil.No maternal mortality and clinical signs or behavioral changes were observed in treated female rats as compared to control. No effect on body weight and feed consumption changes were observed in treated female rats as compared to control. Similarly, no effect number of corpora lutea, number of live fetuses per litter, litter size, mean fetal body weight, or mean crown-rump length was observed in treated rats. Ratio of male and female pups at the 1000 mg/ kg/day dose level was significantly different from the control group but was not considered treatment related. Slight but significant increase in relative liver weight of treated female rats was observed as compared to control. In addition, No developmental parameter such as viability, fetal body weight and external malformations were observed in treated fetuses as compared to control. One fetus with bent limb bones, two fetuses from different mothers with microphthalmia and two other fetuses with omphalocele were observed at 1000 mg/kg/day and single fetus with multiple malformations were observed at 300 mg/kg/day in treated fetuses as compared to control. The incidence of developmental variations in the treated litters was not significantly increased over the control incidence. They occurred in low frequency and were distributed randomly across the Quat-Silsesquioxane treated and control groups. Therefore,NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawley female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
Reference
TABLE 1
Summary of Maternal Body Weight Gain, Food Consumption, and Liver Weights
|
Dose levels (mg/kg/day) |
||||
Gestation day |
0 |
100 |
300 |
1000 |
|
|
Mean body weight change (g) |
||||
0-6 |
26 ± 7a |
25 ±7 |
27 ±7 |
29 ±8 |
|
6-9 |
3 ± 8 |
3 ± 8 |
7±7 |
6 ± 8 |
|
9-12 |
16 ± 10 |
19 ±6 |
15 ± 4 |
15 ± 9 |
|
12-16 |
27 + 7 |
26 ± 12 |
22 ± 8 |
22 ± 11 |
|
16-20 |
59 ± 11 |
61 ± 17 |
62 ± 13 |
60 ± 15 |
|
0-20 |
131 ± 19 |
133 ±25 |
132 ± 19 |
132 ±25 |
|
0-20 adjustedb |
61 + 13 |
62 ± 14 |
62+13 |
66 ± 13 |
|
Mean food consumption (g/dam/day) |
|||||
0-6 |
21.5 + 2 |
21.5 ±2 |
22.3 ±2 |
22.0 ± 4 |
|
6-9 |
17.8 ± 4 |
15.2 ±3* |
17.9 ± 3 |
19.9 ± 8 |
|
9-12 |
17.9 ± 2 |
17.9 ± 2 |
19.9 ±3* |
21.2 ±8 |
|
12-16 |
19.8 ± 2 |
21.1 ±5 |
20.4 ± 3 |
20.2 ±4 |
|
16-20 |
27.3 ± 2 |
27.4 ±3 |
26.2 ±6 |
28.0 ±2 |
|
0-20 |
21.3+1 |
21.2 ± 2 |
21.7 ± 2 |
22.5 ± 3 |
|
Mean maternal liver weight(20 days of gestation) |
|||||
Absolute (g) |
15.4 + 2.9 |
15.3 ±2.9 |
16.1 ±2.6 |
16.5 ±2.5 |
|
Relative (%) |
4.4 ± 0.4 |
4.4 ± 0.3 |
4.5 ±0.3 |
4.6 ± 0.2* |
|
aMean ± SD.
bDam body weight minus the uterus and its contents.
* Significantly different from controls; ANOVA, Welch Test, P < 0.05
TABLE 2
Summary of Observations at Time of Cesarean Sections
|
Dose levels (mg/kg/day) |
|||
|
0 |
100 |
300 |
1000 |
Animals examined at cesarean sections |
25 |
25 |
25 |
25 |
Nongravid |
7 |
7 |
5 |
4 |
Gravid |
18 |
18 |
20 |
21 |
Dams with resorptions only |
0 |
0 |
0 |
0 |
Dams with viable fetuses |
18 |
18 |
20 |
21 |
Viable fetuses/dama |
13.3 ±2.7 |
13.3 ± 3.3 |
13.2 ± 4.2 |
12.4 ± 4.0 |
Postimplantation loss/dama |
1.1 ±0.8 |
0.6 ± 0.61 |
1 5 ± 2.31 |
0.8 + 0.8 |
Total implantation/dama |
14.4 ±2.5 |
13.9 ± 3.5 |
14.7 ± 3.4 |
13.2 ± 4.4 |
Corpora lutea/dama |
17.8 ±3.3 |
15.8 ± 2.6 |
17.7 ± 2.9 |
16.2 ± 3.2 |
Mean crown-rump length (cm) |
3.5 ±0.1 |
3.5 ± 0.2 |
3.5 ± 0 1 |
3.5 ± 0 1 |
Group mean uterine weights (g) |
70.1 ±14.1 |
71.3 ±17.7 |
70.3 ±21.2 |
66.5 ± 18.2 |
Group mean preimplantation loss (%) |
18.8 |
12.0 |
17.2 |
18.2 |
Group mean postimplantation loss (%) |
7.7 |
4.4 |
9.9 |
6.1 |
Mean fetal body weight (g) |
3.4 ±0.2 |
3.5 ± 0.5 |
3.4 ± 0.2 |
3.4 + 0.3 |
Fetal sex ratio—m:f (%) |
44:56 |
49:51 |
50:50 |
55:45* |
aMean ± SD.
* Significantly different; x2. P * 0.05.
TABLE 3
Summary of the Incidence of Fetal Malformations*
|
Dose levels (mg/kg/day) |
|||
|
No. examined |
|||
Litters |
18 |
18 |
20 |
21 |
Fetuses externally |
240 |
238 |
263 |
260 |
Fetuses viscerally |
119 |
118 |
132 |
129 |
Fetuses skeletally |
121 |
121 |
132 |
132 |
|
No.of fetuses (No. Of litters) affected |
|||
Malformations observed |
|
|
|
|
Anophthalmia |
1 (1) |
|
|
|
Microphthalmia |
|
|
|
2(2) |
Gastroschisis |
|
|
1(1) |
|
Omphalocele |
|
|
|
2(2) |
Tail agenesis |
|
|
1(1) |
|
Tarsal flexure |
|
|
1(1) |
|
Edema |
|
|
1(1) |
|
Malformed skull bones |
|
|
1(1) |
|
Bent clavicle |
|
|
1(1) |
|
Bent scapula |
|
|
1(1) |
|
Amelia |
|
|
1(1) |
|
Micromelia |
|
|
1(1) |
|
Bent limb bones |
1(1) |
|
|
1(1) |
Vertebral agenesis |
|
|
1(1) |
|
Pelvic malformation |
|
|
1(1) |
|
Total fetuses (litters) with malformations |
2(2) |
0(0) |
1(1) |
5(4) |
* No statistical significance was observed.
TABLE 4
Summary of the Incidence of Fetal Variations*
|
Summary of the Incidence of Fetal Variations* |
|||
|
Dose levels (mg/kg/day) |
|||
|
0 |
100 |
300 |
1000 |
|
No. examined |
|||
Litters |
18 |
18 |
20 |
21 |
Fetuses externally |
240 |
238 |
263 |
260 |
Fetuses viscerally |
119 |
118 |
132 |
129 |
Fetuses skeletally |
121 |
121 |
132 |
132 |
|
No.of fetuses (No. Of litters) affected |
|||
Developmental variations observed |
|
|
|
|
Renal papillae not developed |
|
1(1) |
1(1) |
|
Distended ureter |
|
1(1) |
1(1) |
|
Skull reduced in ossification |
2(1) |
3(2) |
2(2) |
|
Hyoid unossified |
1(1) |
|
1(1) |
1(1) |
25 presacral vertebrae |
|
|
1(1) |
2(2) |
Greater than 13 pairs of full ribs |
|
|
2(2) |
|
14th rudimentary rib(s) |
6(3) |
7(4) |
12(5) |
6(5) |
Bent ribs |
|
1(1) |
|
2(1) |
7th cervical rib |
3(3) |
|
2(2) |
|
Vertebrae reduced in ossification |
1(1) |
|
1(1) |
|
Misaligned sternebra(e) |
8(6) |
6(5) |
8(6) |
4(3) |
Sternebra 5 and/or 6 unossified |
3(5) |
7(6) |
4(4) |
8(6) |
Other sternebra(e) unossified |
1(1) |
|
1(1) |
1(1) |
Ischia reduced in ossification |
1(1) |
|
|
2(1) |
Total fetuses (litters) with developmental variations |
22(12) |
24(11) |
30(14) |
22(12) |
* No statistical significance was observed.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from peer-reviewed journal
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Developmental toxicity:
Data available for target 1-Octadecanaminium- N,N-dimethyl-N-{3- (trimethoxysilyl)propyl}- chloride (CAS no 27668-52-6) for developmental toxicity are summarized as below
In a study conducted by Siddiquiet al(1993),reproductive toxicity was evaluated in Sprague-Dawley female rats by using Quat-Silsesquioxane in the concentration of 0, 100, 300, or 1000 mg/kg/day orally by gavage in corn oil.No maternal mortality and clinical signs or behavioral changes were observed in treated female rats as compared to control. No effect on body weight and feed consumption changes were observed in treated female rats as compared to control. Similarly, no effect number of corpora lutea, number of live fetuses per litter, litter size, mean fetal body weight, or mean crown-rump length was observed in treated rats. Ratio of male and female pups at the 1000 mg/ kg/day dose level was significantly different from the control group but was not considered treatment related. Slight but significant increase in relative liver weight of treated female rats was observed as compared to control. In addition, No developmental parameter such as viability, fetal body weight and external malformations were observed in treated fetuses as compared to control. One fetus with bent limb bones, two fetuses from different mothers with microphthalmia and two other fetuses with omphalocele were observed at 1000 mg/kg/day and single fetus with multiple malformations were observed at 300 mg/kg/day in treated fetuses as compared to control. The incidence of developmental variations in the treated litters was not significantly increased over the control incidence. They occurred in low frequency and were distributed randomly across the Quat-Silsesquioxane treated and control groups. Therefore,NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawley female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
In a study conducted byDupont Chem Co (1992),teratogenicity was evaluated inAlbinofemale rats by using Dow Corninc @Q9-5700 in the concentration of 0, 100, 300 and 1000 mg/kg orally. 1 nongravid rats died at 1000 mg/kg and 1 pregnant rats died at 100 mg/kg as compared to control. No untoward behavioral reactions were observed in treated female rats as compared to control.Similarly,Noeffect on gestation andgross pathological changes were observed in treated female rat as compared to control. In addition, No effect on fetuses Body weight were observed as compared to control. No teratogenic external abnormalities and skeletal and internal developmental effect were observed in treated fetuses as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg for P and F1 generation when Albinofemale rats were treated with Dow Corninc @Q9-5700 orally from gestation days 6 through 15.
Thus, based on the above available data for targetQuat-Silsesquioxane(CAS no 27668-52-6) is likely to be non hazardous as developmental toxicant.
Justification for selection of Effect on developmental toxicity: via oral route:
NOAEL was considered to be 300 mg/kg bw for P generation and 1000 mg/kg for F1 generation when Sprague-Dawley female rats were treated with Quat-Silsesquioxane orally by gavage from day 6 to 15 of gestation.
Justification for classification or non-classification
Based on the above available data for targetQuat-Silsesquioxane(CAS no 27668-52-6) is likely to be non hazardous as reproductive and developmental toxicant.
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