Chrome tungsten titanium buff rutile

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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 nickel and antimony in liver and kidneys, respectively, were measured after 1 and 2 months after exposure

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:

Antimony nickel titanium oxide yellow

EC Number:

232-353-3

EC Name:

Antimony nickel titanium oxide yellow

Cas Number:

8007-18-9

Molecular formula:

(Ti, Sb, Ni) O2

IUPAC Name:

Antimony nickel titanium rutile

Details on test material:

- Molecular formula: Ni Sb Ti O
- Analytical purity: technical grade
- Composition of test material, percentage of components: molarity based: Ti 0.88, Sb 0.05, Ni0.075; weight based: TiO2 80%, Sb2O5 15%, NiO 5%

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 test substance

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

10 ppm

Remarks:

10 ppm in the diet (0.45 mg/kg bw/day)
Basis: nominal in diet

Doses / concentrations 2

Dose / conc.:

100 ppm

Remarks:

100 ppm in the diet (4.5 mg/kg bw/day)
Basis: nominal in diet

Doses / concentrations 3

Dose / conc.:

1 000 ppm

Remarks:

1000 ppm in the diet (45 mg/kg bw/day)
Basis:
nominal in diet

Doses / concentrations 4

Dose / conc.:

10 000 ppm

Remarks:

10000 ppm in the diet (450 mg/kg bw/day)
Basis: nominal in diet

No. of animals per sex per dose:

15 (control: 30). Additionally, 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 activities 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. 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 investigated histopathologically. 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 were analysed for their nickel and antimony contents by AAS. The detection limit for antimony was 5 ppb and for nickel 10 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):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Details on results:

No substance related effects on mortality, clinical signs, body weight, hematology, clinical chemistry, organ weights, gross pathology and histopathology

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

>= 450 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: no effects up to the highest dose tested

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

CHEMICAL ANALYSIS
Antimony
No antimony detectable in liver and kidneys after 1 and 2 months at any dose.
After three months treatment with 10000 ppm TS antimony was detectable in liver (6 ppb) and kidney (5 ppb)of males slighly above the detection limit and in females at levels of 6 (liver) and 10 (kidney)ppb