Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate

Carcinogenicity

Description of key information

There are many studies are available for Acid Yellow 23 with negative results.

Acid Yellow 23 is not consider as carcinogen.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: primary reference of Colipa report n. C29

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Deviations:

not specified

GLP compliance:

no

Species:

rat

Strain:

other: Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

Charles River CD rats obtained from Charles River Breeding Laboratories, Wilmington, MA, were 63-70days old at the initiation of the F 0 phase of the study. They were housed individually in stainless-steelcages except during the mating, lactation and post-weaning periods of the in utero phase. Each rat was identified with a metal ear tag. If this was lost the animal was re-tagged and/or toe- clipped. The ratswere housed in an environmentally controlled room (20-21°C, 40-60% relative humi- dity) on a 12-hr light/dark cycle. Food was available ad lib. Control animals received Purina Rodent Chow (Ralston Purina Co. Inc., St Louis, MO) and the treated animals received the appropriate dietary admixture.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on exposure:

Fresh diets were prepared and presented weekly. The diets were blended in a twin-shell blender and assays were per- formed to determine the homogeneity and stability of the tested substance in the prepared diets prior to the start of the study. Dietary concentrations of the compound were determinedweekly during the first 13 wk of the study, and then monthly thereafter. Analyses of the basic feed for heavy metals, chlorinated hydrocarbons and aflatoxin were conducted on all lots of feed used during the study. These analyses demonstrated that the basic feed contained acceptably low levels of contaminants, that the diets were prepared properly, and that the dietary content of the test material was stable.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 years

Frequency of treatment:

daily administration

Dose / conc.:

0 other: %

Remarks:

no adminstration

Dose / conc.:

0.1 other: %

Dose / conc.:

1 other: %

Dose / conc.:

2 other: %

Dose / conc.:

5 other: %

Remarks:

high dose

No. of animals per sex per dose:

In the "in utero" phase / original study: 360 rats (60/sex/group) In the "in utero" / high dose study: 120 (60/sex/group) In the chronic phase: 70/sex/group

Control animals:

yes, concurrent no treatment

Details on study design:

Three control groups containing 360 rats (60/sex/group) received the basal diet only. Female rats were weighed on gestation days 0, 4, 14 and 21.

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

At the termination of the study 128 rats from the original study and 58 from the high-dose study were killed, whereas 472 rats from the original study and 182 rats from the high-dose study were killed in extremis, or died spontaneously or accidentally during the studies. There were no compound-related effectson the number of rats surviving.Increased mortality among the male rats of control group 1 and female rats of the 1.0% group resulted in the termination of the original study at wk 113 and 114 for males and females, respectively. The mortality among these two groups appeared to be random and not associated with the consumption of the tested substance.

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

Group mean body weights at termination were generally similar for control and treated rats in the originalstudy except for males and females at the 1.0% dietary level in which decreases in group mean bodyweights were noted. The difference between the females treated at the 1.0% level and the controls wasstatistically significant (P <0.01). The rats (both male and female) from the high-dose study exhibited a statistically significant decrease in group mean body weights at termination.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Food consumption was similar for control and treated rats in the original study. Food consumption among the high-dose rats was generally higher than that of the controls although the increases were not statistically significant.

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Ophthalmoscopic examinations at most examination intervals revealed focal and diffuse retinopathy, conjunctivitis, uveitis, and cataracts in rats of all groups. None of these findings was compound related.

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Few of the haematological, clinical chemistry and urinalysis parameters differed significantly between the control and treated animals, and none of the differences appeared to be compound related.

Clinical biochemistry findings:

not specified

Urinalysis findings:

no effects observed

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

Localized hair loss (due to friction against the cage) and nasal and ocular discharge occurred in low incidence throughout the study and were similarly distributed in control and treated rats. A yellow tint to the fur was noted in all treated animals and the faeces of the 1.0, 2.0 and 5.0% treated rats were yellow

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Description (incidence and severity):

In the ten rats of each sex from each group killed and necropsied after 1 yr on test in both studies, there were no compound-related gross or microscopic changes.

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Histological evaluation revealed a variety of lesions, including neoplasms among the control and treated rats in the original and high-dose studies. These lesions were present in similar incidences in control and treated rats and appeared to be spontaneous. None of the lesions were determined to be rela ted to the administration of the tested substance.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

Histological evaluation revealed a variety of lesions, including neoplasms among the control and treated rats in the original and high-dose studies.These lesions were present in similar incidences in control and treated rats and appeared to be spontaneous..None of the lesions were determined to be related to the administration of the tested substance.

Details on results:

No compound-related gross changes, including organ-weight effects, were noted during the gross necropsies performed on all animals that died on test or that were killed at study termination in both studies.

Dose descriptor:

NOAEL

Effect level:

2 641 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: overall evaluation

Dose descriptor:

NOAEL

Effect level:

3 348 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: overall evaulation

Conclusions:

Not carcinogen

Executive summary:

Based on the test results, the incidence of lesions is the same both in the test and control group and appears to be spontaneous.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 641 mg/kg bw/day

Study duration:

chronic

Species:

rat

System:

other: different organ evaluated

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The are many available carcinogenicity studies for Acid Yellow 23.

Six carcinogenicity studies reviewed by JEFCA are reported in Efsa report on Acid Yellow 23 but there are more recent studies reviewd in 2002.

The pubblication of Maekawa et al (1987) and Borzelleca and Hallagan (1988) were evaluated for the assessment of the carcinogenicity.

No evidence of carcinogenicity was observed in all of the studies.

Acid Yellow 23 does not have a potential to induce benign or malignant neoplasias.