Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Principles of method if other than guideline:
This study were operated/conducted in accordante with the requirements and recommendations of the Animal Welfare Act (P.L. 89-544 as amended by P.L. 91-579 and P.L. 94-279), and other applicable federal, state and local laws, regulations and policies.
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of the test substance used in the study report: C-800
white clumped powder; 99.7% active ingredient

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Age at initiation of exposure (approx.): 7 weeks
Weight at initiation of exposure: 260 - 303 g
Animals were acclimated for 2 weeks. All animals were examined by the staff veterinarian during the acclimation period.
Each rat was identified with a metal ear tag bearing its unique Bio/dynamics, Inc. animal number. If the tag was lost, it was replaced. In addition, each cage was provided with a cage card which was color-coded for dose level identification and contained the project number, animal number, sex and exposure group information.
Husbandry during non-exposure periods: The animals were doubly housed in stainless steel wire mesh cages during the 1st week of the acclimation period and individually housed thereafter. A standardized laboratory animal diet as well as drinking water were offered ad libitum.
The day/night rhythm was 12 h dark and 12 h light. Room temperature 19 - 26°C, relative humidity: 29 - 70%.
Husbandy during exposurep eriods: The animals were individually housed in stainless steel, wire mesh cages within a 1000 liter glass and stainless steel exposure chamber. Food and drinkg water were not available. Room temperature 29 - 28°C, relative humidity: 10 - 70%.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
Exposure level was determined gravimetrically or spectrophotometrically and particle size distribution measurements (average mass median aerodynamic diameter, (MMAD)) were made in regular intervals throughout the study.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 d
Frequency of treatment:
6 h/d, 5 d/w
Doses / concentrations
Remarks:
Doses / Concentrations:
42 mg/m3
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
The animals were observed for clinical findings of intoxication, detailed physical examinations were conducted weekly, body weight was determined weekly, hematology measurements were performed an all animals at week 4 and clinical chemistry (serum GPT, alkaline phophatase, albumin, total bilirubin, gamma glutamyl transpeptidase) was performed at week 1 (5 animals/group) and at week 4 on all animals.
Sacrifice and pathology:
After 4 weeks of exposure all animals were sacrificed, selected organs (brain, kidneys, liver, lungs, testes, spleen) were weighed and relative (in relation to the brain) organ weights were calculated, complete gross postmortem examinations and histological examination after hematoxylin and eosin staining of selected tissues (kidneys, liver, lungs, spleen, testes/epididymides) were conducted an all animals.

Results and discussion

Results of examinations

Details on results:
Particle size distribution measurements for the test substance revealed an MMAD of 11 u with a geometric standard deviation of 2.0. Over 48% of particles were found to be 10 u or less, indicating that the test atmosphere was only moderately respirable in size.
The only significant deviation observed was a significant decrease of albumin after the first week of exposure. After 4 weeks the albumin values had returned to normal values. This finding was considered of unclear toxicological significance.

Effect levels

Dose descriptor:
NOAEC
Effect level:
42 mg/m³ air
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Dust exposure of 42 mg/m3 of the test substance did not lead to mortality nor to any other treatment-related findings after 28 days of exposure. Thus, this dose level can be considered as a no observed effect level (NOEL) under the conditions of the present investigation.