Chromium trioxide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Well reported literature study, but with a non-standard design. Findings are consistent with those in other similar studies.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

carcinogenicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited animal numbers and non-standard exposure pattern

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

The incidences of respiratory tract tumours were investigated in female mice exposed to chromic acid mist at a concentration of 1.81 mg/m3 for
periods of 60 minutes twice a week for 12 months.

GLP compliance:

no

Remarks:

literature study

Species:

mouse

Strain:

C57BL

Sex:

female

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Mice were exposed for two periods of 60 minutes per week for 12 months.

Frequency of treatment:

Mice were exposed for two periods of 30 minutes per week for 12 months

Post exposure period:

Exposed animals were terminated at 8-12 months (23 mice including 3 decedents), or 12-18 months (20 mice including 3 decedents). Controls were terminated at 18 months (20 mice).

Remarks:

Doses / Concentrations:
1.81 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

43 exposed animals, 20 controls

Control animals:

yes, concurrent no treatment

Relevance of carcinogenic effects / potential:

A marginally elevated incidence of lung tumours was seen in exposed animals. The incidence was not statistically significant compared to controls,
however the sensitivity of the study may be limited by group size and exposure pattern.

Dose descriptor:

LOAEC

Effect level:

1.81 mg/m³ air

Sex:

female

Basis for effect level:

other: Signs of local toxicity (irritancy/corrosivity) and some indications of carcinogenicity were observed at the single exposure level in this study.

Irritant and corrosive effects of chromic acid were demonstrated in exposed animals by increased occurrence of perforated nasal septum, tracheal and bronchial hyperplasia and emphysema. Metaplastic changes in the lung were also more frequent in exposed animals (4/23 and 5/20) compared to controls (1/20). Only one lung tumour was found in exposed animals: an adenoma in the 12-18 month group. No tumours were seen in controls.

Conclusions:

Some evidence of an increased incidence of lung tumours was seen under the conditions of this study.

Executive summary:

Female mice were exposed by inhalation to chromic acid mists at a concentration of 3.63 mg/m3 for two periods of 30 minutes per week for 12 months. Exposure was found to cause corrosive and irritant effects on the respiratory tract. The incidence of lung tumours was marginally elevated in exposed mice.

Data source

Reference

Reference Type:

publication

Title:

Effects of chromium compounds to the respiratory system. Part 5.

Author:

Adachi S

Year:

1987

Bibliographic source:

Jpn J Ind Health 1987 (29); 17-33

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study investigated toxicity to the respiratory tract following repeated inhalation exposure to chromic acid mist for two 60 minute periods a week for 8-12 months.

GLP compliance:

no

Remarks:

Literature study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chromic acid

EC Number:

231-801-5

EC Name:

Chromic acid

Cas Number:

7738-94-5

Molecular formula:

CrH2O4

IUPAC Name:

dihydroxy(dioxo)chromium

Constituent 2

Reference substance name:

Chromium trioxide

EC Number:

215-607-8

EC Name:

Chromium trioxide

Cas Number:

1333-82-0

Molecular formula:

CrO3

IUPAC Name:

trioxochromium

Details on test material:

Chromic acid (mist); aqueous chromium trioxide

Test animals

Species:

mouse

Strain:

C57BL

Sex:

female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: Data are not reported, but other studies by the same authors report particles of inhalable size (predominantly <5 µm)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Mice were exposed for 8-12 months.

Frequency of treatment:

Mice were exposed for two periods of 60 minutes per week

Doses / concentrations

Dose / conc.:

1.81 mg/m³ air (analytical)

No. of animals per sex per dose:

Exposed animals were terminated at 8-12 months (23 animals, including 3 decedents) or 12-18 months (20 animals including 3 decedents). Twenty unexposed controls were terminated at 18 months.

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

Examinations focused on local effects on the respiratory tract

Results and discussion

Results of examinations

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Irritant and corrosive effects in the respiratory tract (perforated nasal septum, tracheal and bronchial epithelial hyperplasia, emphysema) occurred in treated animals

Effect levels

Dose descriptor:

LOAEC

Effect level:

1.81 mg/m³ air (analytical)

Based on:

test mat. (total fraction)

Sex:

female

Basis for effect level:

other: Single exposure level: irritant and corrosive effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Exposure to chromic acid mist at the exposure level equivalent to 1.81 mg Cr/m3 for 8-12 months was found to induce changes consistent with irritation and corrosion in the respiratory tract of female mice.

Executive summary:

Female ICR mice were exposed to chromic acid mist at a concentration equivalent to 1.81 mg Cr/m3 for two 60 -minute periods a week for 8 -12 months. Exposure was found to induce changes consistent with irritation and corrosion in the respiratory tract.