Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Remarks:
other: subchronic with evaluation reproductive organs
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Meets generally accepted scientific standards with acceptable restrictions. No information was provided about whether concentrations of the test substance remained constant during the exposure periods. Changes in food or water consumption were not reported. No information concerning behavioral changes. No ophthalmological examinations were performed. No clinical biochemistry or hematological parameters were examined. No urinalysis was performed. Limited number of organs and tissues were examined at necropsy. No information on whether a vehicle was used to generate exposure concentrations. The absorbed fraction of Ni cannot be quantified from this study.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Lung toxicity after 13-week inhalation exposure to nickel oxide, nickel subsulfide or nickel sulfate hexahydrate in F344/N rats and B6C3F1 mice.
Author:
Dunnick, J.K., M.R. Elwell, J.M. Benson, C.H. Hobbs, F.F. Hahn, P.J. Haly, Y.S. Cheng, and A.F. Eidson.
Year:
1989
Bibliographic source:
Fundamental and Applied Toxicology. 12:584-594.
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A standard Test Guideline was not specified in this study.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): nickel sulphate
- Molecular formula (if other than submission substance): not different than submission substance
- Molecular weight (if other than submission substance): not different than submission substance
- Smiles notation (if other than submission substance): not different than submission substance
- InChl (if other than submission substance): not different than submission substance
- Structural formula attached as image file (if other than submission substance): not different than submission substance
- Substance type: soluble, metallic, oxidic, and sulphidic Ni
- Other details on test material not reported or not applicable

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Frederick Cancer Research Facility, Frederick, Maryland, USA.  
- Age at study initiation: 7-8 weeks old
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: housed individually
- Diet (e.g. ad libitum): available during non-exposure
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25 deg C
- Humidity (%): 17-45%
- Air changes (per hr): 12 +/- 2 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hr light/dark

IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Multi-tiered inhalation chambers were used for each exposure. The chambers had total volumes of 1.0 m3 and 1.7 m3.
- Method of holding animals in test chamber: no data
- Source and rate of air: no data
- Method of conditioning air: no data
- System of generating particulates/aerosols: Nickel sulfate aerosol was produced using a nebulizer. The aerosol was passed through a K-85 discharger and mixed with diluting air for each concentration of nickel sulphate tested.
- Temperature, humidity, pressure in air chamber: no data
- Air flow rate: no data
- Air change rate: 10-14 changes per hour
- Method of particle size determination: using cascade impactors
- Treatment of exhaust air: not reported

TEST ATMOSPHERE
- Brief description of analytical method used: concentrations was monitored by taking three 2-hr filter samples during 6 hr daily exposure. Mean daily exposure was calculated from the filter samples. Aerosol size distribution was determined using cascade impactors.

VEHICLE (if applicable)
- water
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Exposure concentrations were monitored by taking 3 filter samples during the 6-hour exposure  periods (1 sample every 2 hours). Target concentrations were 0, 0.12, 0.25, 0.5, 1.0, and 2.0 mg nickel  sulfate hexahydrate/m3, or 0, 0.02, 0.05, 0.1, 0.2, and 0.4 mg Ni/m3.   
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours/day, 5 days/week, for 13 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/m³ air (nominal)
Remarks:
test material
Dose / conc.:
0.12 mg/m³ air (nominal)
Remarks:
test material
Dose / conc.:
0.25 mg/m³ air (nominal)
Remarks:
test material
Dose / conc.:
0.5 mg/m³ air (nominal)
Remarks:
test material
Dose / conc.:
1 mg/m³ air (nominal)
Remarks:
test material
Dose / conc.:
2 mg/m³ air (nominal)
Remarks:
test material
No. of animals per sex per dose:
10 males/10 females/dose
Details on study design:
- Dose selection rationale: The highest concentrated tested (0.4 mg Ni/m3) had previously been found to cause changes in body weight gains and induce lung lesions. Control animals received filtered air only.

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Effect level:
0.45 mg/m³ air (nominal)
Based on:
element
Sex:
male/female
Basis for effect level:
other: No effects on sperm morphology, number or motility, or vaginal cytology were observed at highest exposure level.

Observed effects

No effects on sperm morphology, number or motility, or vaginal cytology were observed after 13 weeks exposure at highest exposure level of 0.45 mg Ni/m3 of nickel sulphate hexahydrate

Applicant's summary and conclusion

Conclusions:
Assessed by independent reviewer