Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Inappropriate dosing: IP Injection. No information on test material.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals 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.