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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
2 and 13 weeks
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
3000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
6000 ppm
Basis:

Remarks:
Doses / Concentrations:
12500 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
25000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
50000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes, plain diet

Results and discussion

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
< 3 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Bone Marrow (Hyperplasia), Spleen (Congestion, Hematopoietic cell proliferation, Pigment),
Dose descriptor:
LOAEL
Effect level:
>= 6 000 mg/kg diet
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Liver (Hematopoietic cell proliferation)
Dose descriptor:
LOAEL
Effect level:
>= 12 500 mg/kg diet
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Kidney (Pigment), Liver (Pigment)
Dose descriptor:
LOAEL
Effect level:
>= 6 000 mg/kg diet
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Kidney (Protein Casts)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
LOAEL < 3000 mg/kg diet
Executive summary:

2- Week Studies:

Groups of five rats and five mice of each Sex were given feed containing 0,6,000,12,500, 25,000, 50,000, or 100,000 ppm C.I. Pigment Red 3 for 2 weeks. No chemical-related deaths occurred in rats or mice. Final mean body weights of exposed rats and male mice were lower than controls; female mice that received 6,000 and 50,000 ppm had significantly increased final mean body weights compared to that of the controls. The feed consumption of treated rats and mice was slightly greater than that of the controls, suggesting that C.I. Pigment Red 3 had no adverse effects on the feed palatability. Dose-related decreases in erythrocyte counts and hematocrit values and an increase in reticulocyte counts were observed in rats. Changes in these Parameters were observed in mice, but there were no clear, dose-related trends.

13-Week Studies:

Groups of ten rats and ten mice of each Sex were given feed containing 0, 3,000, 6,000, 12,500, 25,000, or 50,000 ppm C.I. Pigment Red 3 for 13 weeks. The dose levels selected were 0, 6000, 12500 and 25000 ppm. This resulted in calculated time weighted average daily dose levels of 272, 567, and 1219 mg/kg b.w. in males and 323, 686, and 1388 mg/kg in females at 6000, 12500 and 25000 ppm, respectively. No chemical-related deaths were observed in rats or mice. The final mean body weights of exposed female rats were significantly lower than that of the controls; the final mean body weights of exposed male rats and exposed mice were similar to controls. There were significant increases in relative liver and kidney weights of exposed male rats. Increases in the relative liver weights in mice did not occur with a dose-related trend and thus they were not considered related to chemical administration. Sites for the toxicity of C.I. Pigment Red 3 were the bone marrow, kidney, liver, and spleen in rats. Lesions observed in rats included bone marrow hyperplasia, congestion and hematopoietic cell proliferation of the spleen, and iron-positive pigmentation of the spleen, kidney, and liver. Sites for the toxicity of C.I. Pigment Red 3 in mice were the liver, kidney, and spleen in males and the liver and spleen in females. Lesions noted among mice in the spleen were hematopoietic cell proliferation and iron-positive pigmentation. In the liver, there was hematopoietic cell proliferation in male and female mice. Cytomegaly occurred in the renal tubule epithelium of the male mouse kidney.