Nickel bis(dihydrogen phosphate)

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

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

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Inappropriate dosing: IP Injection. No information on test material.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Toxicity to heavy metals and relationship to seizure thresholds.

Author:

Adler MW, Adler CH

Year:

1977

Bibliographic source:

Clin. Pharmacol. Therap. 22, 774-779.

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

NiSO4

IUPAC Name:

nickel(2+) sulfate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Weight: 275-325 g
Environmental Conditions: 22 +/- 1 deg C, 50 +/- 10% relative humidity, standard 24 hr light cycle
Food and water provided ad libitum.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Details on exposure:

I.P. Injections given once daily in a volume of 0.5 ml for 2 days

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not reported

Duration of treatment / exposure:

2 days

Frequency of treatment:

1 per day

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:
NiSO4: 10, 30, 40, 50 mg/kg/day Ni Acetate: 10, 30, 40, 50 mg/kg/day
Basis:
nominal conc.

No. of animals per sex per dose:

8-9

Control animals:

yes, concurrent vehicle

Details on study design:

To evaluate seizures, a 10% flurothyl solution in 95% ethanol (v/v) inudcer was provided at a constant rate of infusion of 0.103 ml/min
by a Harvard infusion pump until the onset of clonic conclusion.

Examinations

Examinations:

Two tailed T-test for independent samples.
LD50 calculated by linear extrapolation

Positive control:

none reported

Results and discussion

Details on results:

Endpoint LD50: 35 — 40 mg/kg/d (Ni Sulphate)
Endpoint LD50: 35 — 40 mg/kg/day (Ni acetate)
Mortality:
NiSO4: 100% survival <=30 mg/kg/day, 8/9 died at 50 mg/kg
Ni Acetate: 100% survival <=30 mg/kg/day, 6/8 died at 40 mg/kg, 7/8 died at 50 mg/kg
Body weight: Significant reduction of body weight in the 30 mg/kg/day dose group (NiSO4 and Ni Acetate)
Other findings: Significant increase in seizure threshold at the 30 mg/kg/day dose group (NiSO4 and Ni Acetate)

Applicant's summary and conclusion

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.