PIGMENT RED 5021B

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-10-08 to 1991-11-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline 407 (adopted 1981) study, GLP compliant. Acceptable deviations from OECD guideline 407 adopted 2008: less organs weighed and microscopically examined, no specific neurobehavioural examinations performed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

adopted 1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Version / remarks:

of April 25, 1984

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

IN-LIFE DATES: From: October 8, 1991 To: November 6, 1991 (treatment groups), December 4, 1991 (recovery groups)

no further information available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % carboxymethylcelluloseand 0.1% Tween 80 in distilled water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Suspensions of the test article in the selected vehicle at the appropriate concentrations were freshly prepared every day immediately prior to the dosing of the animals and administered within about 2 hours.

VEHICLE
- Amount of vehicle (if gavage): 10 mL/bw

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Control analyses of the test article concentration in the vehicle were carried out at all dose levels on samples collected once per experimental week. The samples were collected after administration, immediately deep frozen and sent to the analytical laboratories. The samples were analysed spectrophotometrically. The analytical results confirmed the nominal concentrations.

Duration of treatment / exposure:

28 days

Frequency of treatment:

Once a day

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 200, 1000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

5 animals per sex per dose, additional 5 animals per sex at 0 and 1000 mg/kg bw/d (recovery group animals)

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Dose levels were fixed based on the results of an acute oral toxicity study in rats (LD50 > 2000 mg/kg bw) and a repeated dose oral toxicity study in rats (a 14-day range finding study in which the test article was tolerated up to a daily dose of 1000 mg/kg bw/day
for 14 days without significant toxicological consequences).

- Post-exposure recovery period in satellite groups: 4 weeks

Positive control:

Not required

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: examination was carried out daily.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: examination was carried out daily.

BODY WEIGHT: Yes
- Time schedule for examinations: The weight of all animals was recorded individually at weekly (midweek) weighing sessions. The first weights were recorded during the acclimatisation period.

FOOD CONSUNPTION AND EFFICIENCY: yes
- - Time schedule: weekly
The food consumption ratios were calculated as mean of individual ratios according to the following formula: weekly food consumption (g)/ midweek bodyweight (g) x 1000/7

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
No further information available.

CLINICAL CHEMISTRY: Yes
No further information available.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
At autopsy the following weights were recorded from all animals: body (exsanguinated), brain, liver, kidneys, adrenals, ovaries/testes


HISTOPATHOLOGY: Yes
After fixation, organ samples of all animals of the treatment groups were taken, embedded in paraplast, sectioned at 3-5 microns, stained with hematoxylin and eosin, and subjected to a microscopical examination:
spleen
heart
liver
kidney, both
adrenal gland, both
any organ with gross lesions

In addition, liver identified as possible target organ was examined microscopically in all animals of the recovery groups.

Statistics:

Each treated group i s compared to the control group by Lepage's two-sample test. This test is a combination of Wilcoxon and Ansari-Bradley statistics, i . e . a combined test for location and dispersion. The Lepage t est has a good power against the more general alternative that the distributions differ not only
in location but also in dispersion. Increasing or decreasing trends in location from control to the highest dose group are tested by Jonckheere's test for ordered alternatives. This test is sensitive to monotone dose-related treatment effects.

Results and discussion

Effect levels

1

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

2

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

CLINICAL SIGNS AND MORTALITY

No death occurred during the study and no relevant treatment-related clinical signs were observed during the study.

BODY WEIGHT AND WEIGHT GAIN

No relevant differences in bodyweight development were recorded

during the study.

FOOD EFFICIENCY

No relevant differences in mean food consumption were recorded for treated and control animals and mean food consumption ratios for treated groups were comparable to those of the control groups.

HAEMATOLOGY

The treatment had no effect on hematological parameters investigated.

CLINICAL CHEMISTRY

No evidence of a treatment-related effect on blood chemistry parameters was apparent.

ORGAN WEIGHTS

The analysis of organ weights revealed no relevant differences between treated and control groups.

GROSS PATHOLOGY and HISTOPATHOLOGY:

All macroscopical and microscopical findings were considered to be unrelated to the treatment.