o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

OECD SIDS o-TOLUIDINE
5. TOXICITY ID: 95-53-4
DATE: 07.01.2005
154
f: 0.5, 6.2, 14.5, 19.0
all differencies were statistically significant at 5% level by Mann- Whitney
U criteria
- Histopathology (no details reported):
urothelial hyperplasia: 6000 ppm: females: mild; males: minimal
Thickening of the urothelia layer:
3000 ppm: females and males, minimal, sporadically;
6000 ppm, all males minimal
- Cell proliferation: biologically significant increase:
3000 ppm in females (0.38 vs 0.08 of controls)
6000 ppm in both sexes (m: 1.42 vs 0.47 of controls;
f: 2.55 vs 0.08 of controls)
- Urinary NAAC (N-acteyl-4-amino-m-cresol) levels:
values after 24 h on day 14 (low, mid, high dose):
males: 65, 249, 402 mg/l; females: 52, 179, 251 mg/l
In controls no NAAC detected
Urinary excretion of NAAC was positively correlated with
urinary bladder cell proliferation.
This relationship suggests that NAAC may be useful as a
urinary biomonitor for exposure to the test substance.
- UDS: positive, for further information see chapter 5.6
Test condition : TEST ORGANISMS
- Age: approx. 59 days
- Weight at study initiation means: males 179.5-196.2g;
females 118.1-137.3g
- Number of animals: 10 animals were treated,
5/10 were used for the UDS-test
ADMINISTRATION /EXPOSURE
- Vehicle: purina certified rodent diet
- Doses: 500, 300, 6000 ppm corresponding an estimated
- daily intake of 40.4, 238, and 449 mg/kg/day in males and
- 43.5, 251, and 481 in females (not adjusted for the stability of the test
substance in the diet). Test substane concentration from the 7-day stability
samples were 58.6 % (500 ppm, 68 % (3000 ppm) and 66.8 % (6000 ppm)
CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: during weighing (3 times per week)
- Mortality: twice daily during the week, once daily on
weekends
- Body weight: yes, 3 times per week
- Food consumption: yes, individually per week
NECROPSY: at the end of the treatment period rats were sacrificed. For
each animal the bladder and sections of the duodenum (as appropriate (as
positive control for the immunohistopathological staining technique)) were
removed and processed for the various toxicity evaluations.
HISTOPATHOLOGICAL EVALUATION
The histopathological examination was limited to the urinary bladder
(microscopic changes in urothelium), as this study was primarily conducted
to investigate urinary bladder toxicity
OTHER EXAMINATIONS:
- Blood sampling for Methemoglobin analyses immediately after sacrifice
- Urinary bladder cell proliferation:
immunohistochemically stained slides - approx. 3000 epithelial cells were
counted and the labeling index was determined
- Unscheduled DNA synthesis (UDS) was conducted with further 5 animals
per dose group: see Chapter 5.6
- Urinary metabolite quantitation:
urine samples were collected at days 6-7 and 13-14 during
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