ALFERROCK

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

A 13-week toxicity study of simultaneous administration of cochineal and aluminum potassium sulfate in rats

Author:

Kawasaki, Y.

Year:

1994

Bibliographic source:

Eisei Shikensho Hokoku (1994), 112, 48-56

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

7784-24-9

Cas Number:

7784-24-9

IUPAC Name:

7784-24-9

Constituent 2

Reference substance name:

aluminium potassium sulfate dodecahydrate

IUPAC Name:

aluminium potassium sulfate dodecahydrate

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): aluminium potassium sulfate*24 H2O (A) and Cochineal (C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 weeks

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

N.A.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

3 other: %

Remarks:

Aluminium potassium sulfate

Doses / concentrations 2

Dose / conc.:

1.5 other: %

Remarks:

simultaneous administration of Aluminium potassium sulfate with 1.5% Cochineal.

Doses / concentrations 3

Dose / conc.:

0.75 other: %

Remarks:

simultaneous administration of Aluminium potassium sulfate with 0.75% Cochineal.

No. of animals per sex per dose:

15 rats/group (7 rats/group sacrificed after 4 weeks)

Control animals:

yes

Details on study design:

Cochinal (C), a scarlet material extracted from the powdered pregnant insect Dactylopius Coceus Costa is used as a color food additive in the form of aluminium lakes. A 13 week subchronic toxicity study was conducted to investigate the effects of simultaneous administration of C and aluminium potassium sulfate (A). Male and female Wistar rats were given diets containing 0.75% A and 0.75% C (1.5% AC), 1.5% A and 1.5 % C (3% AC), 3% C alone and 3% A alone.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: once a week

FOOD CONSUMPTION: Yes
- Time schedule for examinations: once a week

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 4 and 13 weeks
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 7/group after weeks, 8/group after 13 weeks
- Parameters checked: rbc, hgb, pcv, mcv, mch, mchc, plt, wbc

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after 4 and 13 weeks
- Animals fasted:No data
- How many animals: 7/group after weeks, 8/group after 13 weeks
- Parameters checked: total protein, blood urea nitrogen, phospholipid, triglycerides, total cholesterol, alanine aminotranferase, glutamate dehydrogenase, gamma-glutamyltransferase, calcium

Sacrifice and pathology:

ORGAN WEIGHTS
Organ weights were measured after 4 and 13 weeks for the following organs:
male: liver, kidney, spleen, testis and adrenal
females: liver,kidney, spleen, ovary and adrenal

HISTOPATHOLOGY: Yes
Histopathology was conducted after 4 and 13 weeks for the following organs: pituitary gland, lung, liver and kidney

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A slight body weight gain decrease was observed for the male rats in the 3% A dose group

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Serum levels of phospholipids, triglycerides and total cholesterol in male rats and TG in female rats fed 3% C, 3% A or 3% AC were significantly decreased at the 13th week

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Serum levels of phospholipids, trigylcerides and total chlosterol in male rats and triglycerides in female rats were decreased in comparison to the control after treatment with 3% aluminium potassium sulfate dodecahydrate

Urinalysis findings:

not examined

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:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

30 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects reported at maximum daily dose

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In this 13-week oral toxicity study treament with 3% (w/w) aluminium potassium sulfate dodecahydrate in the diet led to a decrease in body weight gain after 13 weeks in male rats and to a change of certain clinical chemistry marker in male and female rats. As no effects were seen for clinical signs of toxicity, mortality, histopathologic lesions, haematology or organ weights the NOAEL can be considered to be 30.000 ppm.

Executive summary:

In a 13-weeks subchronic oral toxicity study (similar to EU method B.26) aluminium potassium sulfate dodecahydrate was administered orally via the diet to 15 male and female Wistar rats up to a concentration of 30000 ppm (3% w/w). The animals were treated with the test item 7 days per week for a period of 13 weeks, whereas 7 animals/sex/group were sacrificed after 4 weeks. The treatment led to a decrease in body weight gain after 13 weeks in male Wistar rats. Additionally, serum levels of phospholipids, trigylcerides and total chlosterol in male rats and triglycerides in female rats were decreased in comparison to the control after treatment with 3% aluminium potassium sulfate dodecahydrate. As no effects were seen for clinical signs of toxicity, mortality, histopathologic lesions, haematology or organ weights the NOAEL can be considered to be 30.000 ppm.