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Carcinogenicity

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Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The unusual study design, 78 week testament followed by a 20 week treatment free 'recovery period', the exclusion of animals which died pre-term as well as deficits in reporting make it impossible to assess the validity of the study results

Data source

Reference
Reference Type:
publication
Title:
Carcinogenicity Testing of the Cosmetic Dye: D&C Red No. 36
Author:
Kupradinun P, Rienkijakarn M, Tanyakaset M, Tepsuwan A, Kusarnran WR
Year:
2002
Bibliographic source:
Asian Pacific Journal of Cancer Prevention 3: 55-60,2002

Materials and methods

Test guideline
Qualifier:
no guideline followed

Test material

Constituent 1
Chemical structure
Reference substance name:
1-[(2-chloro-4-nitrophenyl)azo]-2-naphthol
EC Number:
220-562-2
EC Name:
1-[(2-chloro-4-nitrophenyl)azo]-2-naphthol
Cas Number:
2814-77-9
Molecular formula:
C16H10ClN3O3
IUPAC Name:
1-[(2-chloro-4-nitrophenyl)diazenyl]-2-naphthol
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
78 weeks
Post exposure period:
20 weeks treatment free "recovery period"
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
2000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes, plain diet

Results and discussion

Applicant's summary and conclusion

Conclusions:
The results of the present study thus demonstrated that C.I. Pigment Red 4 (=D&C Red No. 36) at the concentrations of 1,000 ppm and 2,000 ppm in the diet is not carcinogenic either to male or female Wistar rats.
Executive summary:

In this study groups of 50 male and 50 female Wistar rats were administered D&C Red No. 36 (Warner Jenkinson Company, NJ, USA; Purity > 95%) at dietary dose levels of 0, 1000, and 2000 ppm for 78 weeks (estimated daily dose: 50 and 100 mg/kg b.w.). At week 98 all surviving animals were killed and various organs were sampled and stored in formalin. The organs sampled included at least lung, liver, spleen, kidney, urinary bladder, mammary gland and thyroid gland. Survival of rats was not affected by treatment. The number of survivors at termination (week 98) was 50, 48 and 48 in males and 50, 47, and 50 in females at 0, 1000, and 2000 ppm, respectively. The 7 animals which died were excluded from evaluation since they died before week 40. Body weight development was not affected in males but slightly, but statistically significant lower in treated females when compared to the control. Besides body weight data no information is available to assess the systemic toxicity caused by PR4 and thus obtain an indication on the bioavailability of the pigment.

Tumor incidences were reported for liver, thyroid, adrenals, urinary bladder, and mammary gland (Table 4). The incidence of benign tumors was low (£4%) in most tissues and not indicative of a treatment-related effect. Higher tumor incidences were only observed in the liver and mammary gland. The mammary tumor incidence in females and of liver tumors in males was not indicative of an adverse effect. In females the incidence of “liver tumors' was dose-dependently increased (Please note: the incidences reported also include hyperplastic nodules!). This increase was however not statistically significant. The incidence of malignant tumors was likewise low and did not indicate a relation to treatment.

 

Based on the data presented the authors conclusion was: “The results of the present study thus demonstrated that D&C Red No. 36 at the concentrations of 1,000 ppm and 2,000 ppm in the diet is not carcinogenic either to male or female Wistar rats. While the occurrence of benign liver tumors in female rats may be related to dye treatment, the lack of any apparent dose-dependence or any statistically significant difference from the control group (P = 0.06) suggests that this is unlikely.”

A treatment-related increase of her tumors in females is questionable since a) various types of her tumors and pre-neoplastic lesions were lumped together and b) the historical background of liver tumors in the strain of rats used in that laboratory is not known.

Furthermore, the unusual study design, 78 week testament followed by a 20 week treatment free 'recovery period', the exclusion of animals which died pre-term as well as deficits in reporting make it impossible to assess the validity of the study results.