Calcination products of titanium dioxide, tin monoxide, zinc oxide and dihydrogen wolframate

Immunotoxicity

Administrative data

Endpoint:

immunotoxicity: short-term oral

Type of information:

experimental study

Adequacy of study:

supporting study

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:

Immunotoxic Effects of Sodium Tungstate Dihydrate on Female B6C3F1/N Mice When Administered in Drinking Water

Author:

Rachel P. Frawley, Matthew J. Smith, Kimber L White Jr., Susan Elmore, Ron Herbert, Rebecca Moore, Lauren M. Staska, Mamta Behl, Michelle J. Hooth, Grace E. Kissling, and Dori R. Germolec

Year:

2016

Bibliographic source:

J Immunotoxicol. 2016 September; 13(5): 666–675

Materials and methods

Principles of method if other than guideline:

28-day Drinking water exposure of female mice with evaluation for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

disodium dioxotungstenbis(olate) dihydrate

EC Number:

600-275-2

Cas Number:

10213-10-2

Molecular formula:

Na2WO4* 2 H2O

IUPAC Name:

disodium dioxotungstenbis(olate) dihydrate

Test material form:

solid - liquid: aqueous solution

Details on test material:

Sodium tungstate dihydrate (STD, Na2WO4·2H2O, CAS #10213-10-2, Lot #12330JO) was obtained through an NTP analytical chemistry contract at Battelle (Columbus, OH). Stability data provided by Battelle indicated that formulations of STD in tap water were stable for at least 42 days at both 5°C and at room temperature.

Test animals

Species:

mouse

Strain:

B6C3F1

Remarks:

/N

Sex:

female

Details on test animals or test system and environmental conditions:

At 8–9 wk of age (17–26 g), the mice were weighed, randomized via an Apple computer-generated randomization procedure, identified by tattoo, and placed on treatment

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

125 mg/L drinking water

Doses / concentrations 2

Dose / conc.:

250 mg/L drinking water

Doses / concentrations 3

Dose / conc.:

500 mg/L drinking water

Doses / concentrations 4

Dose / conc.:

1 000 mg/L drinking water

Doses / concentrations 5

Dose / conc.:

2 000 mg/L drinking water

No. of animals per sex per dose:

8

Control animals:

yes, concurrent vehicle

Examinations

Observations and clinical examinations performed and frequency:

Mice were weighed prior to initiation of the study, and on Days 1, 8, 15, 22 and 29.

Sacrifice and pathology:

Organ weights were obtained for the liver, spleen, lungs, thymus, kidneys, and adrenal glands.

Histopathology: Liver, spleen, lungs, thymus, kidneys, adrenals, bone marrow (femur), gastrointestinal (GI) tract with Peyer’s patches, and mesenteric lymph nodes (LN), submandibular LN, and popliteal lymph nodes

Other examinations:

Hematology parameters evaluated included: erythrocyte and leukocyte numbers, leukocyte differentials, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet number.

Positive control:

Positive controls used in these studies included rabbit anti-asialo GM1 antibody (AAGM1, Wako BioProducts, Richmond, VA), maleic vinyl ether (MVE; Hercules Incorporated, Wilmington, DE), and cyclophosphamide (CPS; Sigma, St. Louis, MO),. AAGM1, 0.2 ml of a 10% (v/v) solution in sterile physiological saline administered by intra-peritoneal (IP) injection 24 hr prior to necropsy, was the positive control for natural killer (NK) cell activity. MVE, 50 mg/kg administered in a single intravenous (IV) injection 24 hr prior to necropsy, was the positive control for mononuclear phagocytic system (MPS) activity. CPS, given at a dose of 50 mg/kg by IP injection once daily during the last 4 days of the exposure period (last 5 days for the keyhole limpet hemocyanin [KLH] study), was the positive control for all other assays.

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

500 mg/L drinking water

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Under conditions of co-exposure to an immune-stimulating agent, the substance may modulate the normal cell-mediated immune response.

Any other information on results incl. tables

Exposure in drinking water for 28 days at doses of 125–2000 mg/L had limited effect on humoral and innate immunity, on developing hematopoietic cells in the bone marrow and on unstimulated splenocyte phenotypes in B6C3F1/N mice. Exposure may have decreased the functional activity of T-lymphocytes at 1000 mg STD/L, as evidenced by the reduction of TCTL activity, and the proliferative response to allogeneic leukocytes and the anti-CD3 antibody, while increasing the activity at lower doses. These data indicated that, under conditions of co-exposure to an immune-stimulating agent, such as tumor cells or genetically dissimilar leukocytes, STD may modulate the normal cell-mediated immune response.