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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
repeated dose toxicity: inhalation
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.