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EC number: 946-329-1 | CAS number: -
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Starting on day 0 of gestation, streptozocin-induced diabetic and nondiabetic control rats were fed a low-Zn diet (4.5 µg/g diet), an adequate-Zn diet (24.5 µg/g diet), or a high-Zn diet (500 µg/g diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20 and examined.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Simonsen, Gilroy, CA
- Females: virgins
- Weight at study initiation: (P1) Females: 220-240 g
- Housing: housed individually in suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum (deionised water)
- Acclimation period: adaption to diet and light-dark cycle for 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23 °C
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on mating procedure:
- - M/F ratio per cage: not specified
- Length of cohabitation: not specified
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentrations of Zn, Cu, Mn, Fe, Mg and Ca were confirmed by flame atomic acsorption spectroscopy (AAS IL-551, Instrumentation Laboratories, Wilmington, MA).
- Duration of treatment / exposure:
- After mating, the rats were assigned to one of the following diets ad libitum for 20 days:
1) low Zn diet containing 4.5 µg/g diet
2) adequate Zn diet containing 24.5 µg/g diet
3) high Zn diet containing 500 µg/g diet. - Frequency of treatment:
- daily with food
- Dose / conc.:
- 4.5 other: µg/g diet
- Remarks:
- further referred to as "low-Zn diet"
- Dose / conc.:
- 24.5 other: µg/g diet
- Remarks:
- further referred to as " adequate-Zn diet"
- Dose / conc.:
- 500 other: µg/g diet
- Remarks:
- further referred to as "high-Zn diet"
- No. of animals per sex per dose:
- not mentioned in publication
- Control animals:
- no
- Details on study design:
- This study was designed to assess the effect of maternal Zn intake in diabetes-induced rats. For this WoE, only the results of the diabetes' control group is of interest. Consequently, the results of the diabetes group will be not discussed herein.
- Parental animals: Observations and examinations:
- BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined on a daily basis - Postmortem examinations (parental animals):
- SACRIFICE
- Maternal animals: All animals were sacrificed
EXAMINATION OF...
- number of live, dead, and resorbed fetuses
- maternal livers and kidneys
- maternal plasma and tissue analyzed for Zn, Cu, Mn, Fe, Ca, and Mg concentrations by flame AAS - Statistics:
- Data were analyzed with two-way analysis of variance. The significance of observed differences among the groups was evaluated with Duncan's multiple-range test. Values of P < 0.05 were considered statistically significant
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- "Among the control groups, dams fed the low-Zn diet had significantly less body weight gain on days 18-20 of pregnancy than controls fed the adequate- or high-Zn diets. There was no effect of dietary Zn on maternal weight gain in the diabetic groups."
- Food consumption and compound intake (if feeding study):
- not specified
- 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:
- no effects observed
- Description (incidence and severity):
- No diet-related differences in the concentrations of liver and kidney Mn, Cu, Zn, Ca, or Mg were found. Dietary Zn did not affect maternal kidney metallothionein concentrations. As dietary Zn increased, plasma Zn concentrations also increased. Placental concentrations of Cu, Zn, Fe, and Ca were similar among the groups,
- 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:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Increasing dietary Zn tended to lower the resorption frequency.
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Effect level:
- 4.5 mg/kg diet
- Based on:
- element
- Sex:
- female
- Basis for effect level:
- other: resorption frequency
- Remarks on result:
- other: "low-Zn diet"
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Effect level:
- 24.5 mg/kg diet
- Based on:
- element
- Sex:
- female
- Basis for effect level:
- other: resorption frequency
- Remarks on result:
- other: "adequate-Zn diet"
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Effect level:
- 500 mg/kg diet
- Based on:
- element
- Sex:
- female
- Basis for effect level:
- other: resorption frequency
- Remarks on result:
- other: "high-Zn diet
- Critical effects observed:
- no
- Remarks on result:
- not measured/tested
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetuses from dams fed the low-Zn diet had low liver Zn levels compared with those fed the adequate- and high-Zn diets."
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- "Maternal dietary Zn had an affect on fetal outcome. Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet. Fetuses receiving the adequate-Zn diet had 11% more calcified sternal sites than fetuses fed the low-Zn diet. No further improvement in calcification with the high-Zn diet was observed. Ossification of fetal vertebrae, metacarpals, and anterior phalanges was lowest in the low-Zn group and increased compared with fetuses from the adequate-Zn group. Ossification of these three sites did not improve in group fed the high-Zn diet. Dietary Zn had only a modest effect on fetal malformation frequency, there was no further improvement in the frequency of fetal abnormalities when the high-Zn diet was fed."
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Generation:
- F1
- Effect level:
- 4.5 mg/kg diet
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: body length, Ossification of fetal vertebrae, fetal malformation frequency
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Generation:
- F1
- Effect level:
- 24.5 mg/kg diet
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: body length, Ossification of fetal vertebrae, fetal malformation frequency
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Generation:
- F1
- Effect level:
- 500 mg/kg diet
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: body length, Ossification of fetal vertebrae, fetal malformation frequency
- Critical effects observed:
- no
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- no
- Conclusions:
- Maternal animal:
"Among the control groups, dams fed the low-Zn diet had significantly less body weight gain on days 18-20 of pregnancy than controls fed the adequate- or high-Zn diets. There was no effect of dietary Zn on maternal
weight gain in the diabetic groups."Increasing dietary Zn tended to lower the resorption frequency. No diet-related differences in the concentrations of liver and kidney Mn, Cu, Zn, Ca, or Mg were found. Dietary Zn did not affect maternal kidney metallothionein concentrations. As dietary Zn increased, plasma Zn concentrations also increased. Placental concentrations of Cu, Zn, Fe, and Ca were similar among the groups,
Fetuses:
„Fetuses from dams fed the low-Zn diet had low liver Zn levels compared with those fed the adequate- and high-Zn diets. Maternal dietary Zn had an affect on fetal outcome. Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet. Fetuses receiving the adequate-Zn diet had 11% more calcified sternal sites than fetuses fed the low-Zn diet. No further improvement in calcification with the high-Zn diet was observed. Ossification of fetal vertebrae, metacarpals, and anterior phalanges was lowest in the low-Zn group and increased compared with fetuses from the adequate-Zn group. Ossification of these three sites did not improve in group fed the high-Zn diet. Dietary Zn had only a modest effect on fetal malformation frequency, there was no further improvement in the frequency of fetal abnormalities when the high-Zn diet was fed." - Executive summary:
Starting on day 0 of gestation, rats were fed a low-Zn diet (4.5 mg/kg diet), an adequate-Zn diet (24.5 mg/kg diet), or a high-Zn diet (500 mg/kg diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20. Maternal dietary Zn had a minor effect on fetal malformation frequency. The adequate- and high-Zn diets improved fetal length and weight.
Maternal animal:
"Among the control groups, dams fed the low-Zn diet had significantly less body weight gain on days 18-20 of pregnancy than controls fed the adequate- or high-Zn diets. There was no effect of dietary Zn on maternal weight gain in the diabetic groups."Increasing dietary Zn tended to lower the resorption frequency. No diet-related differences in the concentrations of liver and kidney Mn, Cu, Zn, Ca, or Mg were found. Dietary Zn did not affect maternal kidney metallothionein concentrations. As dietary Zn increased, plasma Zn concentrations also increased. Placental concentrations of Cu, Zn, Fe, and Ca were similar among the groups.
Fetuses:
„Fetuses from dams fed the low-Zn diet had low liver Zn levels compared with those fed the adequate- and high-Zn diets. Maternal dietary Zn had an affect on fetal outcome. Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet. Fetuses receiving the adequate-Zn diet had 11% more calcified sternal sites than fetuses fed the low-Zn diet. No further improvement in calcification with the high-Zn diet was observed. Ossification of fetal vertebrae, metacarpals, and anterior phalanges was lowest in the low-Zn group and increased compared with fetuses from the adequate-Zn group. Ossification of these three sites did not improve in group fed the high-Zn diet. Dietary Zn had only a modest effect on fetal malformation frequency, there was no further improvement in the frequency of fetal abnormalities when the high-Zn diet was fed."
Data source
Reference
- Reference Type:
- publication
- Title:
- Influence of Maternal Dietary Zn Intake on Expression of Diabetes-Induced Teratogenicity in Rats
- Author:
- Uriu-Hare, J. Y., Stern, J. S., Keen, C. L.
- Year:
- 1 989
- Bibliographic source:
- Diabetes, Vol. 38, October 1989
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Starting on day 0 of gestation, streptozocin-induced diabetic and nondiabetic control rats were fed a low-Zn diet (4.5 µg/g diet), an adequate-Zn diet (24.5 µg/g diet), or a high-Zn diet (500 µg/g diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20 and examined
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Zinc
- EC Number:
- 231-175-3
- EC Name:
- Zinc
- Cas Number:
- 7440-66-6
- IUPAC Name:
- zinc
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Simonsen, Gilroy, CA
- Females: virgins
- Weight at study initiation: (P1) Females: 220-240 g
- Housing: housed individually in suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum (deionised water)
- Acclimation period: adaption to diet and light-dark cycle for 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23 °C
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentrations of Zn, Cu, Mn, Fe, Mg and Ca were confirmed by flame atomic acsorption spectroscopy (AAS IL-551, Instrumentation Laboratories, Wilmington, MA).
- Details on mating procedure:
- - M/F ratio per cage: not specified
- Length of cohabitation: not specified
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- After mating, the rats were assigned to one of the following diets ad libitum:
1) low Zn diet containing 4.5 µg/g diet
2) adequate Zn diet containing 24.5 µg/g diet
3) high Zn diet containing 500 µg/g diet. - Frequency of treatment:
- daily with food
- Duration of test:
- 20 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 4.5 other: µg/g diet
- Remarks:
- further referred to as "low-Zn diet"
- Dose / conc.:
- 24.5 other: µg/g
- Remarks:
- further referred to as "adequate-Zn diet"
- Dose / conc.:
- 500 other: µg/g diet
- Remarks:
- further referred to as "high-Zn diet"
- No. of animals per sex per dose:
- not mentioned in publication
- Control animals:
- no
- Details on study design:
- This study was designed to assess the effect of maternal Zn intake in diabetes-induced rats. For this WoE, only the results of the diabetes' control group is of interest. Consequently, the results of the diabetes group will be not discussed herein.
Examinations
- Maternal examinations:
- BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined on a daily basis - Ovaries and uterine content:
- placenta was examined after termination: Yes
- Placental weight: Yes
- Number of implantations: Yes
- Total resorption (%) - Fetal examinations:
- maternal and fetal blood and plasma parameters were examined
-fetal liver was analysed for metallothionein concentration
- External examinations: Yes
Fetal length (cm)
Fetal wt (g)
- Skeletal examinations: Yes
Ossification centers
Sternum
Caudal vertebrae
Metacarpals
Anterior phalanges- Statistics:
- Data were analyzed with two-way analysis of variance. The significance of observed differences among the groups was evaluated with Duncan's multiple-range test. Values of P < .05 were considered statistically significant.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- "Among the control groups, dams fed the low-Zn diet had significantly less body weight gain on days 18-20 of pregnancy than controls fed the adequate- or high-Zn diets. There was no effect of dietary Zn on maternal weight gain in the diabetic groups."
- Food consumption and compound intake (if feeding study):
- not specified
- 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:
- no effects observed
- Description (incidence and severity):
- No diet-related differences in the concentrations of liver and kidney Mn, Cu, Zn, Ca, or Mg were found. Dietary Zn did not affect maternal kidney metallothionein concentrations. As dietary Zn increased, plasma Zn concentrations also increased. Placental concentrations of Cu, Zn, Fe, and Ca were similar among the groups,
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Increasing dietary Zn tended to lower the resorption frequency.
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- effects observed, treatment-related
- Description (incidence and severity):
- Overall, diabetic dams had fewer live pups and more resorptions per litter compared with control dams. Increasing dietary Zn tended to lower the resorption frequency in the diabetic and control groups, although this did not reach statistical significance. The total number of implantation sites per dam were similar among groups.
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- Increasing dietary Zn tended to lower the resorption frequency in the diabetic and control groups, although this did not reach statistical significance.
- Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- Increasing dietary Zn tended to lower the resorption frequency in the diabetic and control groups, although this did not reach statistical significance.
- 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
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Effect level:
- 4.5 mg/kg diet
- Based on:
- element
- Basis for effect level:
- other: resorption frequency
- Remarks on result:
- other: "low -Zn diet
- Dose descriptor:
- conc. level: see 'Remarks'
- Remarks:
- test concentration
- Effect level:
- 24.5 mg/kg diet
- Based on:
- element
- Basis for effect level:
- other: resorption frequency
- Remarks on result:
- other: "adequate Zn-diet"
- Dose descriptor:
- conc. level: see 'remarks'
- Remarks:
- test concentration
- Effect level:
- 500 mg/kg diet
- Based on:
- element
- Basis for effect level:
- other: resorption frequency
- Remarks on result:
- other: "high-Zn diet"
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- 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): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet. - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Dietary Zn had only a modest effect on fetal malformation frequency. Although the percentage of abnormalities was five times higher in the low-Zn control group than in the adequate-Zn group, this was due to a change in the malformation frequency from ca. 1 % (1 of 107) to 5% (5 of 101).
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetuses from control dams receiving the adequate-Zn diet had 11% more calcified sternal sites than fetuses from control dams fed the low-Zn diet. Ossification of fetal vertebrae, metacarpals, and anterior phalanges was lowest in the low-Zn group and increased compared with fetuses from the adequate-Zn group. Ossification of these three sites did not improve in the control group fed the high-Zn diet.
- Visceral malformations:
- not examined
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet.
In the controls, dietary Zn had only a modest effect on fetal malformation frequency. Although the percentage of abnormalities wasfive times higher in the low-Zn control group than in the adequate-Zn group, this was due to a change in the malformation frequency from - 1 % (1 of 107) to 5% (5 of 101).
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- conc. level: test concentration
- Effect level:
- 4.5 mg/kg diet
- Based on:
- element
- Sex:
- not specified
- Basis for effect level:
- other: body length, Ossification of fetal vertebrae, fetal malformation frequency
- Dose descriptor:
- conc. level: test concentration
- Effect level:
- 24.5 mg/kg diet
- Based on:
- element
- Sex:
- not specified
- Basis for effect level:
- other: body length, Ossification of fetal vertebrae, fetal malformation frequency
- Dose descriptor:
- conc. level: test concentration
- Effect level:
- 500 mg/kg diet
- Based on:
- element
- Sex:
- not specified
- Basis for effect level:
- other: body length, Ossification of fetal vertebrae, fetal malformation frequency
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1: Effect of dietary Zn on outcome, skeletal development, and malformation frequency of fetuses from Sprague-Dawley rats
|
Low Zn |
Adequate Zn |
High Zn |
Litters(n) |
9 |
9 |
8 |
Live fetuses/litter |
11.2±1.5*+ |
11.9± 1.5*+ |
12.5±0.9+ |
Implantation sites/litter |
12.9±1.4 |
12.7±1.5 |
13.1±0.7 |
Fetal length (cm) |
3.75±0.03* |
3.90± 0.02+ |
3.91±0.02+ |
Fetal wt (g) |
3.27±0.06* |
3.80±0.05+ |
3.75±0.04+ |
Placental wt (g) |
0.48±0.01* |
0.49±0.01* |
0.48±0.01* |
Resorptions/litter |
1.67± 0.85*+ |
0.78±0.32* |
0.63±0.26* |
Total resorption(%) |
12.9* |
6.1 + |
4.8+ |
Total resorption/total implantation sites |
15/116 |
7/114 |
5/105 |
Fetuses studied for skeletal ossification (n) |
96 |
103 |
98 |
Ossification centers |
|
|
|
Sternum |
5.15±0.13P |
5.79± 0.05# |
5.83± 0.06# |
Caudal vertebrae |
5.22±0.14P |
6.08± 0.06# |
6.02±0.08# |
Metacarpals |
3.73±0.05P |
3.96± 0.02# |
3.95± 0.02# |
Anterior phalanges |
1.10± 0.1P |
1.67± 0.09# |
1.68± 0.08# |
Total malformations(%) |
4.9P |
0.9# |
0.0# |
Malformations/fetuses |
5/101 |
1/107 |
0/100 |
Values are means ± SE. Means not sharing a common superscript are significantly different at P< 0.05.
Applicant's summary and conclusion
- Conclusions:
- Maternal animal:
"Among the control groups, dams fed the low-Zn diet had significantly less body weight gain on days 18-20 of pregnancy than controls fed the adequate- or high-Zn diets. There was no effect of dietary Zn on maternal
weight gain in the diabetic groups."Increasing dietary Zn tended to lower the resorption frequency. No diet-related differences in the concentrations of liver and kidney Mn, Cu, Zn, Ca, or Mg were found. Dietary Zn did not affect maternal kidney metallothionein concentrations. As dietary Zn increased, plasma Zn concentrations also increased. Placental concentrations of Cu, Zn, Fe, and Ca were similar among the groups,
Fetuses:
„Fetuses from dams fed the low-Zn diet had low liver Zn levels compared with those fed the adequate- and high-Zn diets. Maternal dietary Zn had an affect on fetal outcome. Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet. Fetuses receiving the adequate-Zn diet had 11% more calcified sternal sites than fetuses fed the low-Zn diet. No further improvement in calcification with the high-Zn diet was observed. Ossification of fetal vertebrae, metacarpals, and anterior phalanges was lowest in the low-Zn group and increased compared with fetuses from the adequate-Zn group. Ossification of these three sites did not improve in group fed the high-Zn diet. Dietary Zn had only a modest effect on fetal malformation frequency, there was no further improvement in the frequency of fetal abnormalities when the high-Zn diet was fed." - Executive summary:
Starting on day 0 of gestation, rats were fed a low-Zn diet (4.5 mg/kg diet), an adequate-Zn diet (24.5 mg/kg diet), or a high-Zn diet (500 mg/kg diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20. Maternal dietary Zn had a minor effect on fetal malformation frequency. The adequate- and high-Zn diets improved fetal length and weight.
Maternal animal:
"Among the control groups, dams fed the low-Zn diet had significantly less body weight gain on days 18-20 of pregnancy than controls fed the adequate- or high-Zn diets. There was no effect of dietary Zn on maternal weight gain in the diabetic groups."Increasing dietary Zn tended to lower the resorption frequency. No diet-related differences in the concentrations of liver and kidney Mn, Cu, Zn, Ca, or Mg were found. Dietary Zn did not affect maternal kidney metallothionein concentrations. As dietary Zn increased, plasma Zn concentrations also increased. Placental concentrations of Cu, Zn, Fe, and Ca were similar among the groups.
Fetuses:
„Fetuses from dams fed the low-Zn diet had low liver Zn levels compared with those fed the adequate- and high-Zn diets. Maternal dietary Zn had an affect on fetal outcome. Fetal length was shortest in the low-Zn group. With the adequate-Zn diet, linear growth was increased. However, there was no further improvement in length with the high-Zn diet. Fetuses receiving the adequate-Zn diet had 11% more calcified sternal sites than fetuses fed the low-Zn diet. No further improvement in calcification with the high-Zn diet was observed. Ossification of fetal vertebrae, metacarpals, and anterior phalanges was lowest in the low-Zn group and increased compared with fetuses from the adequate-Zn group. Ossification of these three sites did not improve in group fed the high-Zn diet. Dietary Zn had only a modest effect on fetal malformation frequency, there was no further improvement in the frequency of fetal abnormalities when the high-Zn diet was fed."
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