Potassium hydroxyoctaoxodizincatedichromate(1-)

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation, other

Remarks:

other: subacute and subchronic

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across from a highly water soluble chromate, a study following guideline.

Data source

Reference

Reference Type:

publication

Title:

Low level chromium (VI) inhalation effects on alveolar macrophages and immune functions in Wistar rats

Author:

Glaser, U., Hochrainer, D., Klöppel, H., Kuhnen, H.

Year:

1985

Bibliographic source:

Arch Toxicol 57: 250-256.

Materials and methods

Principles of method if other than guideline:

subacute (28 days) and subchronic (90 days) inhalation studies with rats

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium dichromate

EC Number:

234-190-3

EC Name:

Sodium dichromate

Cas Number:

10588-01-9

Molecular formula:

Cr2Na2O7

IUPAC Name:

sodium dichromate

Details on test material:

- Name of test material (as cited in study report): submicron aerosols of sodium dichromate
- Molecular formula (if other than submission substance): Na2Cr2O7

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, F.R. Germany
- Age at study initiation: 3 weeks
- Housing: in groups of ten rats in wire mesh cages
- Diet (e.g. ad libitum): uncontaminated food (Ssniff standard diet) at night only
- Water (e.g. ad libitum): ad libidum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8-23.7
- Humidity (%): 48-56

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Remarks on MMAD:

MMAD / GSD: MMAD 0.20 um, GSD 1.5

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: For generating continuous chromium (VI) aerosols solutions of sodium dichromate were atomized with jet nebulizers. Large particles were deposited in attached cyclons, so that the particles leaving the cyclons were small enough to dry very fast. After discharging these particles by a 85Kr source of radiation (3.7 x 10*8 dps), Na2Cr2O7 aerosol concentrations ranging from 25 to 200 ug/m3 were established by diluting the aerosols with filtered air.
- Method of particle size determination: spiral centrifuge

Duration of treatment / exposure:

subacute 28 days, subchronic 90 days

Frequency of treatment:

22 h a day, 7 days a week

Doses / concentrations

Remarks:

Doses / Concentrations:
25, 50, 100 or 200 ug/m3 Cr
Basis:
nominal conc.

No. of animals per sex per dose:

20 males

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 examined

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:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL CHEMISTRY:
Significant differences (P<0.05) from controls were detected in serum contents of triglyserides and phospholipid in rats exposed to 200 ug/m3 Cr subchronically.

ORGAN WEIGHTS:
Lung and spleen weights were increased significantly (P<0.05) after both subacute and subchronic inhalation of chromate aerosol concentrations above 25 ug/m3 Cr.

IMMUNOLOGY:
Inhalation of low-level chromium (VI) aerosols stimulated humoral immune system, but higher than 100 ug/m3 concentrations depressed the stimulating effect.

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

There were no deleterious effects on behaviour, clinical and pathological appearance of rats. Significantly elevated serum levels of triglycerides and lower contents of phospholipid were seen only in rats exposed to 200 μg/m³subchronically. In both tests above 25 μg/m³Cr concentration, lung and spleen weights were increased significantly. Higher kidney weights were measured only in the rats exposed to 200 μg/m³Cr. Subacute exposure to 25 and 50 μg/m³Cr resulted in activated alveolar macrophages with stimulated phagocytic activities, and significantly elevated antibody responses to injected SRBC's (sheep red blood cells). After subchronic low level exposure, the effect on activation of the alveolar macrophages was more pronounced, and the phagocytic activities were increased. However, at 200 μg/m³Cr, inhibited phagocytic function of the alveolar macrophages was seen. In rats exposed to 200 μg/m³for 42 days, the lung clearance of inert iron oxide was reduced significantly. The humoral immune system was stimulated at subchronic 100 μg/m³Cr concentration, but significantly depressed at 200 μg/m³.

Applicant's summary and conclusion

Conclusions:

Respiratory defence and immunologic functions were stimulated or inhibited depending on dose and time of chromium (VI) inhalation.

Executive summary:

In the subacute (28 days) and subchronic (90 days) inhalation studies of Glaser et al. (1985), 20 male Wistar rats from each group were exposed to submicron aerosols of sodium dichromate (Na₂Cr₂O₇) with the concentrations of 25, 50, 100 or 200 μg/m³

Cr in whole body exposures for about 22 hours a day, seven days a week.

There were no deleterious effects on behaviour, clinical and pathological appearance of rats. Significantly elevated serum levels of triglycerides and lower contents of phospholipid were seen only in rats exposed to 200 μg/m³subchronically. In both tests above 25 μg/m³Cr concentration, lung and spleen weights were increased significantly. Higher kidney weights were measured only in the rats exposed to 200 μg/m³Cr. Subacute exposure to 25 and 50 μg/m³Cr resulted in activated alveolar macrophages with stimulated phagocytic activities, and significantly elevated antibody responses to injected SRBC's (sheep red blood cells). After subchronic low level exposure, the effect on activation of the alveolar macrophages was more pronounced, and the phagocytic activities were increased. However, at 200 μg/m³Cr, inhibited phagocytic function of the alveolar macrophages was seen. In rats exposed to 200 μg/m³for 42 days, the lung clearance of inert iron oxide was reduced significantly. The humoral immune system was stimulated at subchronic 100 μg/m³Cr concentration, but significantly depressed at 200 μg/m³.

In summary, low level exposure to chromium (VI) aerosols increase the respiratory defence and all measured immunological functions in an adaptive manner. However, high exposures inhibit both alveolar phagocytes and immunological functions. Thus, there may be an exposure limit for soluble chromium (VI) above the recommended occupational standards, where potential carcinogenic chromium is a hazard.