Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method/guideline followed: Experimental study to investigate lung effects, not an OECDguideline study.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Duration of treatment / exposure:
4 or 12 weeks for all dose levels
Frequency of treatment:
0.1 ppm for 5 days/week;
0.2 ppm for 5 days/week;
0.5 ppm for 2 days/week;
1.0 ppm for 1 day/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.1 ppm
Basis:
no data
Remarks:
Doses / Concentrations:
0.2 ppm
Basis:
no data
Remarks:
Doses / Concentrations:
0.5 ppm
Basis:
no data
Remarks:
Doses / Concentrations:
1 ppm
Basis:
no data
Control animals:
yes
Positive control:
clean air only 5 days/week for 4 or 12 weeks.

Examinations

Statistics:
Multivariate analysis of variance [MANOVA].

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
no lethality, but change of lung weight and displacement volume.
Mortality:
no mortality observed
Description (incidence):
no lethality, but change of lung weight and displacement volume.

Effect levels

Dose descriptor:
LOAEL
Effect level:
0.1 ppm
Based on:
other: lung weight and displacement volume
Sex:
male

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

NOAEL: None

LOAEL: 0.1 ppm (based on lung weight and displacement volume)

Toxic response/effects by dose level: No lethality was reported in any of the exposed groups

Lung weight and displacement volume were significantly changed at 4 weeks, even at the 0.1

ppm exposure concentration. There was no further change at 12 weeks.

Pulmonary histological changes [thickening and inflammation] were associated with phosgene

exposure, at the terminal bronchiolar regions at 0.1 and 0.2 ppm concentrations, and in the more

peripheral areas at 1.0 ppm [the 0.5 ppm samples were inadvertently lost]. The severity of

changes seemed to depend on phosgene concentrations, and not concentration X time of

exposure.

Histopathology following 4 weeks of clean air recovery after 12 weeks of phosgene exposure

indicated almost complete recovery at 0.1 ppm; the 0.2 ppm group appeared to have resolved

considerably; collagen staining remained at the same level of intensity in the 12 weeks group at

0.2 and 1.0 ppm.

Applicant's summary and conclusion

Conclusions:
The authors conclude that daily exposure to 0.1 ppm phosgene for 6 hrs/day, 5 days/week, for 4
and 12 weeks can cause subtle histological changes in the lungs of rats. Higher concentrations
cause more pronounced effects, which appear to depend more on phosgene concentration than
time of exposure. No lethality was reported.