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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP, non-guideline study. Only summary available, taken from a published regulatory review. Limitations in design and/or reporting but otherwise adequate for assessment.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Screening-level hazard characterisation: Lubricating grease thickeners category
Author:
US Environmental Protection Agency
Year:
2011
Bibliographic source:
Hazard characterisation document
Reference Type:
publication
Title:
Robust summary of information on grease thickeners
Author:
American Petroleum Institute
Year:
2008
Bibliographic source:
Petroleum High Production Volume (HPV) Testing Group (www.petroleumhpv.org/pages/greases)
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Principles of method if other than guideline:
- Method: 4 mL/kg bw lithium 12-hydroxystearate grease in corn oil was administered to 10 male and 10 female rats by oral gavage daily for 90 days.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium 12-hydroxystearate
EC Number:
231-536-5
EC Name:
Lithium 12-hydroxystearate
Cas Number:
7620-77-1
Molecular formula:
C18H36O3.Li
IUPAC Name:
lithium 12-hydroxyoctadecanoate
Test material form:
other: Grease: Lithium 12-hydroxystearate is a thickener at 8.8 % in a base oil
Details on test material:
- Name: Lithium complex grease
- Commercial name: R960002575
- Composition: ~80% base oil, 8.8% lithium 12-hydroxystearate, 1.8% dilithium azelate, ~10% other additives

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age of animals at test initiation: 6 weeks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
No data reported
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data reported
Duration of treatment / exposure:
- Exposure period: 90 days
Frequency of treatment:
- Frequency of exposure: 7 days per week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
250 mg/kg bw/day (62.5 mg/mL)
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
500 mg/kg bw/day (125 mg/mL)
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day (250 mg/mL)
Basis:
nominal in diet
No. of animals per sex per dose:
- Number of animals per dose: 20
- Number of animals per sex: 10 male, 10 female
Details on study design:
- Dose volume: 4 mL/kg bw
- Vehicle control: 10 male and 10 female rats were administered with 4 mL/kg bw corn oil daily for 90 days
Positive control:
No data reported

Examinations

Observations and examinations performed and frequency:
- Observations: Daily observations for clinical signs of toxicity and weekly examinations, including physical examinations, for local and systemic toxicity, pharmacological effects and palpation for tissue masses. Body weights and food intake were recorded weekly.
Sacrifice and pathology:
- Observations: On day 91 after overnight fasting, blood samples were collected and a complete post-mortem examination was conducted. Organ weights were recorded and tissue from high dose and control animals was examined microscopically.
Other examinations:
No data reported
Statistics:
- Statistics: For each time interval, mean values for all dose groups were compared to the control as part of the analysis of body weight, body weight change, food consumption, hematology and clinical chemistry, terminal organ and body weights, organ/body weight ratios and organ/brain weight ratios. Where groups had equal variance, Bartlett's test was performed and parametric procedures used (standard one-way ANOVA using F distribution to assess significance), with unequal variance using nonparametric procedures (Kruskal-Wallis test). Significant differences from the control were determined using a Dunnett's test (parametric) or Dunn test (non-parametric). Trend in dose levels were determined using standard regression techniques with a test for trend and lack of fit (parametric) or Jonckheere's test for monotrend (non-parametric). All tests were conducted at 5% and 1% two-sided risk level apart from Bartlett's test, which was 1% two-sided risk level.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
In mid- and high-dose groups, food intake increased
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Description (incidence and severity):
Prothrombin time and activated partial thromboslastin time increased in treated groups but were within the normal laboratory range and were not considered toxicologically significant
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
The 9% increase in phosphate levels of 500 mg/kg females was not considered to be treatment related
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Organ weights, organ/body weights and organ/brain weights showed no effects
Details on results:
- Necroscopy: There were no macroscopic findings and the microscopic findings were not treatment related

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
other: Grease
Sex:
male/female
Dose descriptor:
NOAEL
Effect level:
88 mg/kg bw/day (nominal)
Based on:
other: lithium 12-hydroxystearate concentration
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The sub-chronic repeated dose oral toxicity of grease containing 8.8 % lithium 12-hydroxystearate in base oil to rats gave a NOAEL of 1000 mg/kg bw/day.
Executive summary:

The sub-chronic repeated dose oral toxicity of grease containing 8.8 % lithium 12-hydroxystearate in base oil to rats gave a NOAEL of 1000 mg/kg bw/day. The repeated dose oral toxicity of lithium 12 -hydroxystearate grease to rats is taken from regulatory review documents (US EPA 2011, API 2008) citing a proprietary test (Huntingdon Life Sciences 1977). No guideline was stated but a standard procedure was used. Only a summary of the study is available, but as the results are taken from a regulatory document, the data are considered adequate for use for this endpoint.

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