Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Standard method, GLP-compliant, adequate experimental details for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Principles of method if other than guideline:
Whole-body exposure to vapour/aerosol. Method generally in accordance with OECD GL 412 (5 days of exposure/week). Groups 2 and 3 exposed to different test samples.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
API 81-09
API 81-10

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: 3.2 - 3.6 microns equivalent aerodynamic diameter (aerosol)
Details on inhalation exposure:
Method of exposure:
Whole-body inhalation
Mass median aerodynamic diameter:
3.2 - 3.6 microns equivalent aerodynamic diameter (aerosol)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Duration of exposure per day: 6 hours
Dosing regime: 5 days/week
No. of animals per sex per dose:
Male: 20 animals at mg/l
Male: 20 animals at .023 mg/l
Male: 20 animals at .024 mg/l
Female: 20 animals at mg/l
Female: 20 animals at .023 mg/l
Female: 20 animals at .024 mg/l
Control animals:
yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
see details on results
Details on results:
Clinical observations:
No exposure-related clinical signs or bodyweight effects
were observed.

Laboratory findings:
No haematology changes were seen in test animals, except for
moderately increased leukocyte counts seen in both sexes of
Group 3 (difference from controls statistically
significant). No differences in serum biochemical
parameters which were considered treatment-related were
reported.

Effects in organs:
Statistically significant absolute and/or relative organ
weight variations were observed in males (Group 2: lung,
brain and body, Group 3: kidney, liver, testis) and in
females (Group 2: lung, liver, pituitary). In the absence
of microscopic or other macroscopic changes, these were
considered not toxicologically significant.

Microscopic pathology revealed changes in the nasal tissues
of Group 2 male and female rats: subacute inflammation of
the anterior nasal cavity mucosa (trace in 7/20 males, 3/20
females and mild in 10/20 males, 12/20 females), with the
nasal epithelium remaining intact. Slight to mild septal
inflammatory change and increased alveolar macrophages
occurred in controls but incidence was slightly increased in
both the Group 2 and Group 3 animals

Effect levels

Dose descriptor:
NOAEL
Effect level:
23 mg/m³ air (nominal)
Based on:
test mat.
Basis for effect level:
other: exposure duration: 6 hours/day

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Reproductive toxicity findings: Statistically significant increase in absolute/relative weight of the testes were recorded, however, no adverse findings were recorded during microscopic examination. Female reproductive organs (uterus, ovary) were also microscopically exmained: no adversed findings recorded.

Applicant's summary and conclusion