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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

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
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Standard method, GLP-compliant, adequate experimental details for assessment

Data source

Reference Type:

Materials and methods

Test guideline
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:
Limit test:

Test material

Details on test material:
API 81-09
API 81-10

Test animals

Crj: CD(SD)

Administration / exposure

Route of administration:
Type of inhalation exposure:
whole body
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:
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:

Results and discussion

Results of examinations

Clinical signs:
no effects observed
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

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:
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