Mill scale (ferrous metal)

Repeated dose toxicity: other routes

Administrative data

Endpoint:

repeated dose toxicity: other route

Remarks:

Marshall, H.E. et al. (1987): 15 weeks

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

other: Not rated according to Klimisch et al.

Rationale for reliability incl. deficiencies:

other:

Remarks:

The reference contained in this summary entry represents in vivo experiments with investigations on repeated dose toxicity with very limited value for risk assessment purposes. The reference does not fulfil the criteria for quality, reliability, and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.

Data source

Reference

Reference Type:

publication

Title:

The stathmokinetic and morphological response of hamster respiratory epithelium to intralaryngeal instillations of saline and ferric oxide

Author:

Marshall HE, Keenan KP, McDowell EM

Year:

1987

Bibliographic source:

Fundam Appl Toxicol 9, 705-714 (1987)

Materials and methods

Principles of method if other than guideline:

Marshall, H.E. et al. (1987):
Test substance: Fe2O3, Pfizer Chemical, Type R3098R, Lot J5
Concentrations: 3 mg/0.2 mL
No. of animals per sex per dose: not specified
Exposure duration/frequency: 1 - 15 weeks, once a week
Negative control: yes
Vehicle control: saline (0.9 % NaCl solution)
Positive control: not specified
Parameters investigated: determination of epithelial mitotic rates of the midtrachea, left intrapulmonary bronchus, and left lung bronchioles 32 hr after the last instillation (1, 5, 10 and 15 weeks of exposure) for each group; histopathological examination of larynx, the mid- and lower trachea, serial cross sections of the left lung, and the center cross section of each lobe ofthe right lung.

Test material

Test material information

Constituent 1

Reference substance name:

Diiron trioxide

Molecular formula:

Fe2O3

IUPAC Name:

Diiron trioxide

Test material form:

solid

Test animals

Species:

other: Marshall, H.E. et al. (1987): male Syrian golden hamster

Sex:

male/female

Administration / exposure

Route of administration:

other: Marshall, H.E. et al. (1987): intralaryngeal instillation

Vehicle:

other: Marshall, H.E. et al. (1987): saline (0.9%)

Results and discussion

Effect levels

Remarks on result:

other: Marshall et al. (1987): no changes in mitotic rates (MR) of trachea or bronchus for any of treated groups but increased MR of bronchioles. Fe2O3 caused bronchioloalveolar hyperplasia after 5 instillations, but less prominent after 10 & 15 instillations.

Applicant's summary and conclusion

Conclusions:

No conclusion can be drawn from the above publication due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.
The reference contained in this summary entry represents in vivo experiments with investigations in repeated dose toxicity with very limited value for risk assessment purposes. The reference does not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X). The information contained therein were included for information purposes only.

Marshal, H.E. et al. (1987):
The non-physiological route of administration via intralaryngeal instillation is not guideline conform and not suitable to assess repeated dose inhalation toxicity. Furthermore, the publication shows significant methodological deficiencies in the experimental set up and documentation. Only male rats and only one dose group were tested which does not allow a dose-response related analysis. Test material was administered only once a week. The number of animals per group was not specified. The experimental design is insufficiently documented and not in accordance with any relevant guideline. Only selected parameters (epithelial mitotic rates for midtrachea, left intrapulmonary bronchus, and left lung bronchioles, and histopathological examination of respiratory tract) were investigated.