Chrome antimony titanium buff rutile

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (non-GLP

Data source

Reference

Reference Type:

publication

Title:

Subchronic Oral Toxicity and Analytical Studies on Nickel Rutile Yellow and Chrome Rutile Yellow with Rats

Author:

Bomhard E et al.

Year:

1982

Bibliographic source:

Toxicol. Letters, 14, 189-194

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

Levels of chromium and antimony in liver and kidneys, respectively, were measured after 1 and 2 months

Principles of method if other than guideline:

Method: T26-16 (comparable to OECD guideline 408)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chrome antimony titanium buff rutile

EC Number:

269-052-1

EC Name:

Chrome antimony titanium buff rutile

Cas Number:

68186-90-3

Molecular formula:

(Ti, Sb, Cr) O2

IUPAC Name:

manganese(4+) trititanium(4+) pentaantimony(3+) chromium(3+) nickel(2+) octadecaoxidandiide

Test material form:

solid

Test animals

Species:

rat

Strain:

other: SPF-derived Wistar TNO W74

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 4-5 weeks
- Housing: macrolon cages
- Individual metabolism cages: no
- Diet (e.g. ad libitum): Altromin
- Water (e.g. ad libitum): tap water


ENVIRONMENTAL CONDITIONS
- reported as "standard conditions"

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Mixing appropriate amounts of powdered food with the test substance

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg diet

Remarks:

0 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

10 mg/kg diet

Remarks:

0.5 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

100 mg/kg diet

Remarks:

5 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg diet

Remarks:

50 mg/kg bw/day

Doses / concentrations 5

Dose / conc.:

10 000 mg/kg diet

Remarks:

500 mg/kg bw/day

No. of animals per sex per dose:

15 (control: 30). 10 animals were used for analytical investigations (control: 20).

Control animals:

yes, concurrent vehicle

Details on study design:

- Post-exposure period: no

Examinations

Observations and examinations performed and frequency:

The animals were observed daily, food consumption and body weight were determined once a week. Haematological, clinical and biochemical investigations (RBC, reticulocytes, platelets, haemoglobin, haematocrit, total and differential WBC, MCV, ALP, GOT, GPT, creatinine, urea, glucose, cholesterol, total plasma and urine proteins, urinalysis) were conducted using recommended methods after one month and at the end of the study on 5 male and 5 female rats of each group. In addition, thromboplastin time and glutamate dehydrogenase activity were measured after 3 months.

Sacrifice and pathology:

All animals, killed at the end of treatment by exsanguination under ether anaesthesia, were subjected to detailed macroscopic examination. Thyroid gland, thymus, heart, lung, liver, spleen, kidneys, adrenals, gonads were weighed and liver, aorta, eyes, intestines, femur, brain, urinary bladder, pituitary, cervical lymph nodes, stomach, oesophagus, epididymides, pancreas, prostate, seminal vesicle, sternum (bone marrow), trachea, uterus, skeletal muscle (M. quadriceps with N. ischiadicus) from 5 males and 5 females of the control and top dose groups were histopathologically examined. Paraffin slices were stained with haematoxylin and eosin. Additional kidney slices were stained by PAS and cryostat slices of liver with Oil Red O.

Other examinations:

After 1, 2 and 3 months liver and kidneys from 5 animals per gender and dose group analysed for their chromium and antimony contents by AAS. The detection limit for antimony was 5 ppb, chromium 2 ppb.

Statistics:

The results of the body and organ weight determination as well as the haematological and clinical chemical data were compared using the U-test according to WiIcoxon (1947). A difference was considered to be significant at P<=0.05.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

no effects observed

Clinical biochemistry findings:

no effects observed

Endocrine findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Details on results:

No substance related effects on mortality, clinical signs, body weight/body weight gain, hematology, clinical chemistry, urinalysis, organ weights, gross pathology and histopathology were observed.

Food consumption was similar in all groups.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical biochemistry

clinical signs

food consumption and compound intake

haematology

mortality

urinalysis

Target system / organ toxicity

Key result

Critical effects observed:

no

Any other information on results incl. tables

CHEMICAL ANALYSIS

Antimony

In males and females the Sb concentrations in liver and kidney were below the detection limit at doses up to 1000 ppm. In the high dose groups the Sb levels slightly increased with exposure duration and reached max. 27 ppb in the liver (3 months) of males (range 15-40 ppb) and 17 ppb in females (kidney 14 ppb in males and 15 ppb in females).

Chromium

No measurable effect on chromium content of liver and kidney at any dose level and exposure duration.