Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Remarks on MMAD:
MMAD / GSD: MMAD= 3.1 - 3.3 um
Duration of treatment / exposure:
28 days
Frequency of treatment:
6 hours per day; 5 days per week
Doses / concentrationsopen allclose all
Dose / conc.:
0.8 mg/m³ air (nominal)
Dose / conc.:
8 mg/m³ air (nominal)
Dose / conc.:
80 mg/m³ air (nominal)
No. of animals per sex per dose:
5 male/female rats
Control animals:
yes

Results and discussion

Results of examinations

Description (incidence and severity):
retarded body weight change (male rats) for 80 mg/m3 group main group
no substance-related effects for females of 80 mg/m3 group post-exposure observation group
no substance-related effects for 8 mg/m3 group main group
no substance-related effects for females of 8 mg/m3 group post-exposure observation group
no substance-related effects for 0.8 mg/m3 groups: main and post-exposure observation groups
Description (incidence and severity):
no substance-related effects for 80 mg/m3 group main group
no substance-related effects for 8 mg/m3 group main group
no substance-related effects for 0.8 mg/m3 groups: main and post-exposure observation groups
Description (incidence and severity):
increased absolute and relative lung weights (males and females) for 80 mg/m3 group main group
trend towards increased absolute and relative lung weigths for females of 80 mg/m3 group post-exposure observation group
increased absolute and relative lung weights for 8 mg/m3 group main group
increased absolute and relative lung weights for females of 8 mg/m3 group post-exposure observation group
no substance-related effects for 0.8 mg/m3 groups: main and post-exposure observation groups
Description (incidence and severity):
no substance-related effects for 80 mg/m3 group main group
no substance-related effects for females of 80 mg/m3 group post-exposure observation group
no substance-related effects for 8 mg/m3 group main group
no substance-related effects for females of 8 mg/m3 group post-exposure observation group
no substance-related effects for 0.8 mg/m3 groups: main and post-exposure observation groups
Description (incidence and severity):
for 80 mg/m3 group main group
lungs:
-        hypertrophy of goblet cells (male and females)
-         interstitial pneumonitis (increased in grading; males and females)
-         increased connective tissue content (male and females)
nasal cavity (level 1):
-         focal metaplasia of the respiratory epithelium (males and females)

increased connective tissue content lungs for females of 80 mg/m3 group post-exposure observation group
no substance-related effects for 8 mg/m3 group main group
no substance-related effects for females of 8 mg/m3 group post-exposure observation group
no substance-related effects for 0.8 mg/m3 groups: main and post-exposure observation groups

Effect levels

Dose descriptor:
NOEL
Effect level:
0.8 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The test substance induced unspecific toxic effects in the nasal cavity and lungs as known from the inhalation of mild irritants. The lesions are reversible except the increase of connective tissue in the lungs which is seen as a reparative process after the inhalation of a mild irritant.
The no-observed-effect-level (NOEL) under the conditions of the test is 0.8 mg/m3.
Executive summary:

The toxic potential of the substance after a repeated exposure via the inhalation route was evaluated according to the OECD Guideline 412. Five male and five female Wistar rats were exposed to four dose levels (0 -0.8 -8 -80 mg/m3) for 28 days. The rats were exposed to the substance 6 hours per day, 5 days per week.

Due to the effects observed in the organ weights ( increased absolute and relative lung weights) in the 8 mg/m3 group main group the NOEL for both males and females is 0.8 mg/m3.