Reaction products of sodium glucoheptonate with zinc sulfate and sodium hydroxide

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:

1989

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

Test material information

Constituent 1

Reference substance name:

Zinc

EC Number:

231-175-3

EC Name:

Zinc

Cas Number:

7440-66-6

IUPAC Name:

zinc

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 / concentrations

Doses / concentrations 1

Dose / conc.:

4.5 other: µg/g diet

Remarks:

further referred to as "low-Zn diet"

Doses / concentrations 2

Dose / conc.:

24.5 other: µg/g

Remarks:

further referred to as "adequate-Zn diet"

Doses / concentrations 3

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)

1

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

2

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"

3

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)

1

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

2

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

3

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."