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Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Version / remarks:
May 12, 1981
Deviations:
yes
Remarks:
A functional test battery was not included.
GLP compliance:
yes
Remarks:
CIBA-GEIGY Limited Short/Long-term Toxicology 4332 Stein / Switzerland
Limit test:
no

Test material

Constituent 1
Reference substance name:
tert-(dodecyl/tetradecyl)-ammonium bis(3-(4-((5-(1,1-dimethyl-propyl)-2-hydroxy-3-nitrophenyl)azo)-3-methyl-5-hydroxy-(1H)pyrazol-1-yl)benzenesulfonamidato)chromate
EC Number:
413-210-6
EC Name:
tert-(dodecyl/tetradecyl)-ammonium bis(3-(4-((5-(1,1-dimethyl-propyl)-2-hydroxy-3-nitrophenyl)azo)-3-methyl-5-hydroxy-(1H)pyrazol-1-yl)benzenesulfonamidato)chromate
Cas Number:
192662-33-2
Molecular formula:
UVCB substance
IUPAC Name:
chromium(3+) 2-methyltridecan-2-aminium bis(4-{2-[5-(2,2-dimethylpropyl)-3-nitro-2-oxidophenyl]diazen-1-yl}-3-methyl-1-(3-sulfamoylphenyl)-1H-pyrazol-5-olate)
Details on test material:
- Substance type: pigment, powder
- Physical state: solid
- Purity test date: no data
- Lot/batch No.: Misch.PA1+3/91
- Expiration date of the lot/batch: January 1997
- Stability under test conditions: yes
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: albino: Tif: RAIf (SPF), hybrids of RII/1 x RII/2
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Production, CIBA-GEIGY Limited, 4332 Stein / Switzerland
- Age at study initiation: approx. 5 weeks at delivery
- Weight at study initiation: 175.0 - 198.2 g in males and 142.0 - 169.9 g in females
- Fasting period before study: no
- Housing: 5/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 16 - 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The substance was weighed on a calibrated Mettler balance. The pulverized food was then homogeneously mixed with the apjpropriate
amounts . Diet was stored deep-frozen in a separate area until use.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 40, 600, 2400 and 12000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
3.7, 50.7, 200.1 and 1075 mg/kg bw
Basis:
other: average calculated intake males based on food intake
Remarks:
Doses / Concentrations:
4.1, 57, 204 and 1141 mg/kg bw
Basis:
other: average calculated intake females based on food intake
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The dose levels were based on the results of the following previously conducted study: Test no. 904252: Acute oral toxicity in the rat Test no. 904287: 14-days range finding study in the rat
- Post-exposure recovery period in satellite groups: 4 weeks

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were checked daily (a.m. and p.m. on working days, a.m. on weekends and holidays), in order to record mortalities, and to allow dead or moribund animals to be submitted to necropsy as soon as possible.
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

WATER CONSUMPTION: Yes
- Time schedule for examinations: weekly

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: all animals of experimental groups I and II at the end of the treatment period, and on all animals of experimental group II at the end of the recovery period
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes
- How many animals: all
- Parameters checked: Erythrocyte Count, Hemoglobin,Hematocrit, Mean corpuscular volume, Reticulocytes, Leucocyte Count, Differential Leucocyte Count, Thrombocyte Count, Prothrombin Time, Methemoglobin

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: all animals of experimental groups I and II at the end of the treatment period, and on all animals of experimental group II at the end of the recovery period
- Animals fasted: Yes
- How many animals: all
- Parameters checked: Glucose, Urea, Creatinine, Total bilirubin, Total protein, Albumin, Globulins, A/G Ratio, Cholesterol, Triglycerides, Sodium, Potassium, Calcium, Chloride, Phosphorus inorganic, Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Gamma-glutamyl
transpeptidase

URINALYSIS:Yes

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:
GROSS PATHOLOGY: Yes
weights were determined for:
brain
liver
kidneys
adrenals
o v a r i e s / t e s t es

HISTOPATHOLOGY: Yes
mesenteric lymph node
stomach
small intestine
large intestine
spleen
mesenteric lymph node
heart
liver
stomach
sraall intestine
large intestine
kidney, both
adrenal gland, both
any organ with gross lesions
Statistics:
For each time point and parameter an univariate statistical analysis was performed. Nonparametric methods were applied,
to allow for non norraal as well as normal data distribution. Each treated group was compared to the control group either by
Lepage's or by Wilcoxon's two-sample test and tested for increasing or d e c r e a s i n g t r e n d s from control up to
the respective dose group by Jonckheere's test for ordered alternatives. The Lepage t e s t is a combination of Wilcoxon
and A n s a r i - B r a d l e y statistics , i . e . a combined test for location and dispersion. The Lepage test has a good power
against the more general alternative that the distributions differ not only in location but also in d i s p e r s i o n . The
Jonckheere testt is sensitive to monotone dose-related effects. Two-sided asymptotic p-values are reported in the "statistics" tables.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined

Effect levels

Dose descriptor:
NOEL
Effect level:
>= 12 000 ppm
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Red discoloration of feces due to the red substance was noted in groups 3, 4 and 5 (600, 2400 and 12000 ppm).

Applicant's summary and conclusion