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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
three-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Long term toxicologic assessment of nickel in rats and dogs.
Author:
Ambrose, A. M. et al.
Year:
1976
Bibliographic source:
Journal of Food Science and Technology 13, 181-187
Reference Type:
secondary source
Title:
Nickel Sulphate, CAS-No.: 7786-81-4, EINECS-No.: 232-104-9, RISK ASSESSMENT Final version March 2008, Chapters 0, 1, 2, 4, 5, 6 & 7 – human health only
Author:
Danish Environmental Protection Agency
Year:
2008
Bibliographic source:
European Union Risk Assessment Report

Materials and methods

Principles of method if other than guideline:
An oral three-generation study in rats was performed, however, examinations were limited. Various indices were calculated (for details see below).
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
10101-97-0
EC Number:
600-152-3
Cas Number:
10101-97-0
IUPAC Name:
10101-97-0
Constituent 2
Reference substance name:
Nickel sulphate
EC Number:
232-104-9
EC Name:
Nickel sulphate
Cas Number:
7786-81-4
IUPAC Name:
nickel(2+) sulfate
Constituent 3
Reference substance name:
nickel (II) sulfate hexahydrate
IUPAC Name:
nickel (II) sulfate hexahydrate
Details on test material:
- Name of test material (as cited in study report): nickel sulfate hexahydrate containing 22.3% nickel by analysis
- Molecular formula (if other than submission substance): NiSO4X6H2O
- Physical state: fines
- Analytical purity: no data

Test animals

Species:
rat
Strain:
other: albino Wistar derived
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Albino Farms, Red Bank, New Jersey
- Age at study initiation: (P) 4 wks; (F1) 2 wks
- Housing: Rats were individually caged.
- Diet (e.g. ad libitum): Radiston Purina, St. Louis, Missouri

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): Stock aqueous solutions of nickel sulfate hexahydrate were prepared in appropriate concentrations so that the addition of 100 mL for each 6 kg of diet resulted in the desired nickel content. Addition of nickel solutions were thoroughly blended into the diet by mixing in a rotary-type blender.
Details on mating procedure:
- M/F ratio per cage: 1:1
- After successful mating each pregnant female was caged (how): individually in a breeding cage
- Any other deviations from standard protocol: Male rats of each group were rotated to a different female on each of three successive 7-day periods. On the 20th mating day alle males were removed.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
11 weeks prior to mating
Frequency of treatment:
continuously for 11 weeks; for F1 litters the treament started after weaning
Details on study schedule:
The parent generation (F0) was mated for F1 litters (For procedure refer to "Details on mating procedure"). Following weaning of F1 litters, surviving F0 rats were sacrificed and autopsied. For the production of F2 and F3 litters, the same procedure was followed.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:

Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 250, 500 and 1000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
30 (20 were used for mating procedures)
Control animals:
yes, plain diet

Examinations

Parental animals: Observations and examinations:
Weekly body weight records were obtained, except during mating through weaning of litters.
Litter observations:
Litters containing more than 10 offsprings were reduced to 10 on day 5.
Postmortem examinations (offspring):
Gross observations on all offspring.
Histopathologic studies were performed on 10 male and 10 female F3 weanlings from each diet level. Tissues included: heart, spleen, kidneys, liver, testes, lung, urinary bladder, stomach, small and large intestine, skeletal muscle, brain, skin, bone marrow, pituitary, thyroid, adrenal, pancreas and gonad
Reproductive indices:
fertility index=(pregnancies/matings)x100
gestation index=(liiters cast/pregancies)x100
Offspring viability indices:
viability index=(live pups at day 5/live pups born)x100
lactation index=(weaned/live pups-dicard on day 5)x100

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Remarks:
fertility
Effect level:
1 000 ppm (nominal)
Sex:
male/female
Basis for effect level:
other: probably corresponding to 52-80 mg Ni/kg bw/day for nickel sulphate
Remarks on result:
other: Generation: all (migrated information)
Dose descriptor:
NOAEL
Effect level:
500 ppm (nominal)
Sex:
male/female
Basis for effect level:
other: body weight

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Body weights of the F0 rats were slightly decreased at the high dose only, with an average decrease of 13% reported for males and 8% reported for females. The fertility index was slightly lower at 250 and 1000 ppm in the F1 generation, and at 1000 ppm in the F2 generation (around 60% compared to 70-79% in the controls), however, the differences were not statistically significant. The fertility index in exposed animals was similar to control values at the high dose in F1, F2 a and b as well as in F3 a and b.

Applicant's summary and conclusion