Toxic Pathologic 2
Toxic Pathologic 2
Toxic Pathologic 2
http://www.elsevier.de/etp
1
Department of Product Safety, Regulations, Toxicology and Ecology, BASF AG, Ludwigshafen, Germany
2
Department of Toxicologic Pathology, Bayer HealthCare AG, Wuppertal, Germany
3
Department of Information Technology and Databases, Fraunhofer Institute of Toxicology and Experimental Medicine,
Hannover, Germany
4
Department of Pathology, Pharmacia Italia S.p.A., Gruppo Pfizer Inc., Nerviano, Italy
5
Department of Pathology, Pfizer, Inc., Groton, CT, USA
6
Department of Toxicology, Hoffmann-LaRoche AG, Basel, Switzerland
7
Department of Pathology/Toxicology, 3M Pharmaceuticals, St. Paul, MN, USA
8
Department of Pathology, Novartis Pharma AG, Basel, Switzerland
9
Department of Pathology, AstraZeneca UK, Alderley Park, Macclesfield, England
Revised guides for organ sampling and trimming in rats and mice
Part 2
A joint publication of the RITA*) and NACAD**) groups
BIRGIT KITTEL1, CHRISTINE RUEHL-FEHLERT2, GERD MORAWIETZ3, JAN KLAPWIJK4, MICHAEL R. ELWELL5,
BARBARA LENZ6, M. GERARD OSULLIVAN7, DANIEL R. ROTH8, and PETER F. WADSWORTH9
With 65 figures
Received: February 24, 2004; Revised: March 20, 2004; Accepted: April 16, 2004
Address for correspondence: GERD MORAWIETZ, Department of Information Technology and Databases, Fraunhofer Insti-
tute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany; Fax: ++49 511 5350 155,
E-mail: morawietz@item.fraunhofer.de
Key words: Trimming; RITA; NACAD; rat; mouse; standardization; guidelines; nasal cavity; nasopharynx; paranasal
sinus; larynx; trachea; bronchus; bronchiole; lung; testis; rete testis; epididymis; prostate; coagulating gland; seminal vesi-
cle; ovary; oviduct; uterus; uterine cervix; vagina; pituitary gland; thyroid gland; parathyroid gland; adrenal gland.
The structures of the palate and the teeth are used for
orientation to achieve transverse sections through the
nasal cavity at certain levels.
In inhalation studies, four transverse tissue levels
should be taken, because the examination of these sec-
tions at defined levels assures consistent recognition of
degenerative and proliferative lesions of all different ep-
ithelial cell types of the nasal cavity and paranasal sinus.
Typically in oral toxicity studies, only the third level is
examined. Neoplastic lesions occur more frequently in
the anterior and middle portions of the nasal cavity,
whereas some non-neoplastic and neoplastic lesions are
observed exclusively in the olfactory epithelium. The
third level includes respiratory and olfactory epithelial
cells. The resulting slices of tissue are embedded with Fig. 3.1b. Nasal cavity, rat, 4 trimming locations.
the rostral face down, because non-neoplastic lesions
have been found to be most severe at the more rostral
borders of the affected epithelium. Slight differences of
the cut level may occur depending on anatomical varia-
tions in different strains.
If more squamous epithelium is required for examina-
tion, a section rostral to level 1 should be performed. For
examination of the olfactory bulb, a section caudal to
level 4 is recommended.
Related references
BROWN 1990, HARDISTY et al. 1999, HARKEMA 1990, Fig. 3.1d. Nasal cavity,
HARKEMA and MORGAN 1996, MORGAN 1991, POPP and rat, location 2. Nd: na-
MONTEIRO-RIVIERE 1985, URAIH and MARONPOT 1990, sopalatine (incisive) duct,
YOUNG 1981 Nl: Nasolacrimal duct.
Fig. 3.1f. Nasal cavity, rat, location 4. Pd: pharyngeal duct Fig. 3.1i. Nasal cavity, mouse, location 2. Ps: paranasal
(nasopharynx). sinus.
Fig. 3.1g. Nasal cavity, mouse, 3 trimming locations. Fig. 3.1j. Nasal cavity, mouse, location 3.
See also:
Thyroid gland
Related references
LEWIS 1991, RENNE et al. 1992, SAGARTZ et al. 1992
Related references
GOPINATH et al. 1987, SCHWARTZ et al. 1991
Related references
BOORMAN et al. 1990a, CHAPIN and HEINDEL 1993,
CREASY and FOSTER 2002, FERM 1987, FOLEY 2001, LAN-
NING et al. 2002, LATENDRESSE et al. 2002, RUSSELL et al.
1990
Fig. 4.1a. Testis, recommended transverse section (green), Fig. 4.1d. Rete testis (R), mouse (V: vasculature, L: Leydig
optional section (blue). cells).
Fig. 4.2a.
Epididymis.
Fig. 4.4e. The urethra is dissected. Fig. 4.4h. Inner aspects of fixed (left) and freshly dis-
sected (right) prostate. Compared to the situation in the
living animal (in situ), the ventral prostate is flipped back.
Fig. 4.4f. Removal of prostate, urinary bladder, and semi- Fig. 4.4i. The prostate lobes are embedded with the
nal vesicles as a unit. outer aspects down, i.e. the dorsolateral lobes with the
dorsal surface down, and the ventral prostate with the
ventral surface down, because this part was flipped back.
Related references Fig. 5.1c. Ovaries (top) and oviducts (bottom). Ovarian
FERM 1987, HEINDEL and CHAPIN 1993, U.S. Food and bursa removed, oviducts separated from ovaries and uterine
Drug Administration 2000, YUAN and FOLEY, 2002 horns.
Related references
FERM 1987, HEBEL and STROMBERG 1986, HEINDEL and
CHAPIN 1993, U.S. Food and Drug Administration 2000,
YUAN and CARLSON 1987, YUAN and FOLEY, 2002
Fig. 5.2d.
Uterine cervix.
Fig. 5.2a. Uterus and vagina, ventral aspect. Fig. 5.2e. Vagina.
Related references
CAPEN 1996a, HEBEL and STROMBERG 1986, MAHLER and Fig. 6.1c. Pituitary gland in situ (Pn: pars nervosa, Pi: pars
ELWELL 1999, OSAMURA 1996, SATOH et al. 1997 intermedia, Pd: pars distalis, Sb: sphenoid bone).
Related references
BOORMAN and DELELLIS 1983, BOTTS et al. 1991,
BOTTS et al. 1994, CAPEN 1996b, CAPEN 1996c, KITTEL Fig. 6.2c. Thyroid gland, longitudinal section, with para-
et al. 1996a, KITTEL et al. 1996b, POZHARISSKI 1990 thyroid gland (Pg).
Related references
FRITH 1996, HEBEL and STROMBERG 1986, NYSKA and
MARONPOT 1999, PAGET and THOMSON 1979