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Diss Factsheets

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is old, but well reported and included the majority of endpoints typical of a guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Whole body inhalation exposures for 5d/wk for 3 weeks.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrabromophthalic anhydride
EC Number:
211-185-4
EC Name:
Tetrabromophthalic anhydride
Cas Number:
632-79-1
Molecular formula:
C8Br4O3
IUPAC Name:
tetrabromophthalic anhydride
Details on test material:
Micronized FM PHT4 was used as the test article.

Test animals

Species:
rat
Strain:
other: Spartan
Sex:
male/female
Details on test animals or test system and environmental conditions:
housed individually in temperature and humidity controlled room. Purina Rat Chow and water available ad libitum.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Each group placed in sealed 59.1 L gass chambers and exposed to a dynamic atmosphere containing the test article or air only. To prevent piling up during the exposure, rats were separated by sex into 4 units of 2 or 3 rats each. Addition of the test material was controlled by a Wright Dust Feeder. Dired and filtered air was passed through the mechanism and directly into the exposure chamber. Air flow was regulated by a flowmeter.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
4 hours, 5 days weekly for 3 weeks.
Frequency of treatment:
5 days weekly for 3 weeks.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 2, 8 mg/L
Basis:
nominal conc.
No. of animals per sex per dose:
5M/5F

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Effect level:
2 mg/L air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: lack of systemic toxicity

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Statistical analysis not performed.

Mean Male Body Weights (g). SD not available.

Group

Day of Test

0

7

14

21

Control

248.4

280.6

308.6

326.0

2 mg/L

247.4

261.0

275.6

307.8

8 mg/L

248.0

274.4

292.8

305.6

Mean Female Body Weights (g). SD not available.

Group

Day of Test

0

7

14

21

Control

226.0

236.2

250.8

259.2

2 mg/L

223.8

220.4

225.0

235.4

8 mg/L

220.8

222.8

232.8

229.0

Mean Weekly Food Consumption by Male Rats (g). SD not available.

Group

Week of Test

0

1

2

3

Control

164.4

186.4

197.2

171.6

2 mg/L

164.4

159.4

173.2

167.6

8 mg/L

163.8

161.8

166.2

154.2

Mean Weekly Food Consumption by Female Rats (g). SD not available.

Group

Week of Test

0

1

2

3

Control

138.6

135.0

148.4

141.0

2 mg/L

141.4

123.8

122.6

119.2

8 mg/L

142.8

120.6

130.6

114.6

Mean Bromine Content (ppm) of Selected Tissues After 21 Exposures, Male and Female Rats Combined. SD not available.

Group

Bromine Content (ppm)

Fat

Liver

Lung

Kidney

Blood

Control

1.50

3.14

11.64

8.23

7.83

8 mg/L

13.54

9.91

38.88

24.79

23.50

Applicant's summary and conclusion

Conclusions:
NOAEC for systemic toxicity was 2 mg/L in this 3 wk inhalation study in rats.
Executive summary:

In a 21 d inhalation study, albino rats were exposed to a micronized form of the test article to atmospheric concentrations of 2 and 8 mg/L. Rats were expsosed for 4 h/d, 5 d/wk for 3 wk. A control group was exposed only to air in the test chambers. Observations were made daily and body weights and food consumption measured weekly. Hemtological, biochemical adn urinalysis studies were conducted at 20 d. Bromine analysis by neutron activation of liver, fat, kidney, lung and blood samples were conducted on samples collected at terminal necropsy.

Clinical observations in the treated groups included salivation, lacrimation, nasal discharge, and nasal porphyrin discharge, Respiratory congestion was observed in one animal at the 8 mg/L dose. No deaths occrred in either the control or treated groups. Slightly lower body weights were observed in treated animals than in the controls (statistical analysis was not performed). Food consumption was similar in control and treated animals. No compound-related hematological, biochemical or urinalysis changes were observed. Bromine analysis of selected tissues and blood by neutron activation indicated increased bromine values in the tissues and blood of animals in the 8 mg/L group over that from the control goup. No compound-related gross lesions were observed. A compound-related decrease in liver weight, and increase in lung weight was observed in both exposure levels. An increase in relative adrenal and thyroid weight in females at 8 mg/L may have been compound-related. Microscopically, an increase in inflamatory lung lesions in both experimental groups may have been compound related. No other lesions related to compound administration were seen in other tissues examined from the 8 mg/L group.