Dialuminium zinc tetraoxide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Remarks:

data from previous registration, not further considered

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well document publication which meets basic scientific principles.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Zinc Feeding and Conception in the Rats

Author:

Pal, N. and Pal, B.

Year:

1987

Bibliographic source:

Internat. J. Vit. Nutr. Res. 57:437-440

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Female rats were exposed either post-coitum from gestational day (GD)1 - GD18 (predevelopmental study; exposure szenario 1) or 21-26 days prior to mating until GD18 (fertility study; exposure szenario 2). On GD18, females were sacrificed and uteri, endometrium, fetuses and placentae were investigated.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

7733-02-2

IUPAC Name:

7733-02-2

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): zinc sulfat, anhydrous, ZnSO4
- Analytical purity: no data

Test animals

Species:

rat

Strain:

other: Charles-Foster

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 120 - 130 days
- Diet: crushed rat feed of Hindustan Lever (India), ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Mixing appropriate amounts with: standard diet, crushed

Analytical verification of doses or concentrations:

no

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: up to 5 days
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy

Duration of treatment / exposure:

(P) females: Day 1-18 of gestation

Frequency of treatment:

continuously

Duration of test:

Day 18 of gestation

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
4000 ppm
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
200 mg/kg bw/day
Basis:
other: calculation based on an estimated food intake of 5g/100g bw/day (WHO estimation)

No. of animals per sex per dose:

12 P males and females

Control animals:

yes, plain diet

Examinations

Maternal examinations:

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 18

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes (pooled data for the respective treatment group)
- Number of implantations: Yes (determined as sum of resorption sites and fetuses)
- Number of resorptions: Yes
- Other: conception rate

Fetal examinations:

OTHER:
Elevated endpoints included number of fetuses, stillbirth and malformations and weighing of fetuses (pooled data for the respective treatment group).

Statistics:

Mean values and standard errors were calculated from the examined parameters. Statistical analyses were performed by FISHER´S one sided t-Test.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes. Remark: 200 mg/kg bw/day: reduced conception incidence, number of fetuses and implantation sites (non-significant)

Details on maternal toxic effects:
A significantly reduced conception incidence was determined in test animals. Specifically, 12/12 females conceived in the control group whereas only 5/12 zinc-exposed females conceived resulting in a mating index of 42%. Further, a non-significant decrease in implantation sites (control: 84; test group: 25) and number of fetuses (control: 84; test group: 24) among the treatment group were reported.

Effect levels (maternal animals)

1

Dose descriptor:

LOAEL

Effect level:

200 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

>= 200 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
BODY WEIGHT (OFFSPRING)
No significant differences in the mean fetal body weights were observed among the control and test group.

GROSS PATHOLOGY (OFFSPRING)
No stillbirth or malformations of fetuses were determined among both test groups.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Table 1: Effects of food zinc supplementation on conception and fetuses

Endpoint	Developmental Toxicity
	Control	200 mg/kg ZnSO4
No. of mated females	12	12
No. of females conceived	12	5**
No. of resorption sites	2	1
No. of stillbirths	0	0
No. of malformation	0	0
No. of fetuses	82	24
Total no. of implantation sites	84	25
Implantation sites/mated females	7	2.1*
Implantation sites/pregnant females	7	5
Weight of fetuses (mean value of the group)	0.70±0.057	0.74± 0.055
Weight of the placenta (mean value of the group)	0.40± 0.022	0.36± 0.012

* = p<0.05, ** = p<0.01

Applicant's summary and conclusion

Conclusions:

Zinc sulfate had no effect on intrauterine development which justifies a respective classification according to Regulation (EC) 1272/2008.