Mill scale (ferrous metal)

Endpoint summary

Description of key information

Skin irritation:  two in vivo skin irritation studies with iron oxides (Fe2O3 and Fe3O4) according to OECD guideline 405 are available. Based on the information from these studies it is concluded that iron oxides are not skin irritating.

Eye irritation:  two in vivo eye irritation studies with iron oxides (Fe2O3 and Fe3O4) according to OECD guideline 405 are available. Based on the information from these studies it is concluded that iron oxides are not eye irritating.

Respiratory irritation: the classification as respiratory irritant is normally covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. Please refer to the endpoint summaries on acute toxicity (endpoint 7.2) and repeated dose toxicity (endpoint 7.5) for further information.

Details on the iron category justification are given in the read-across document attached in IUCLID section 13.2.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

Exposure in the ear of a rabbit

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: The inner side of the second ear was used as a control.

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

24 hrs exposure

Observation period:

168 hrs

Number of animals:

2

Details on study design:

Organisms were kept individually, one female and one male rabbit was exposed. After exposure the ears of the rabbits were rinsed and washed with soap an treated with plant oil.

Irritation parameter:

overall irritation score

Remarks on result:

other: no irritation found

Irritant / corrosive response data:

No irritation found.

Other effects:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

Eisenoxid gelb 920 was not irritating.
According to the EC-Regulation 1272/2008 and subsequent adaptations, the substance does not require classification as irritating to the skin.

Executive summary:

One male and one female New Zealand White Rabbit were exposed to 500 mg FeO(OH) in the ear. Exposure was semiocclusive for 24 hours. There was no irritation observed.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Juli 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981-05-12

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

3 male rabbits were used. The organisms were kept in single cages at temperatures between 19 and 25°C, a relative humidity of 40-60% and a day/night rythm of 12/12 hours. The animals were fed with a standard diet and were allowed to drink tap water ad libitum .

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: 0.2% Na-Polyacrylate, 0.1% Preventol D2 and water (remainder)

Controls:

other: Untreated patches of skin served as a control

Amount / concentration applied:

0.5 ml of the sample

Duration of treatment / exposure:

4 hours.

Observation period:

one,, 24, 48, 72 hours and 7 days

Number of animals:

3 males

Details on study design:

4 hours after the exposure the skin was rinsed with water

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no reaction on the skin for edema. For erythema the results were difficult to judge because the skin was blackened, though after careful observation no irritation marks could be found.

Other effects:

no

Interpretation of results:

GHS criteria not met

Conclusions:

Bayferrox-Schwarz was not irritating.
According to the EC-Regulation 1272/2008 and subsequent adaptations, the substance does not require classification as irritating to the skin.

Executive summary:

Undiluted Bayferrox Schwarz was applied to the shaved skin of three male rabbits (New Zealand White rabbits). Application was with patches and semiocclusive. After 4 hours the patches were removed and the skin was rinsed with water. After 1, 24, 48, 72 and 168 hours the animals were evaluated for erythema and edema; untreated skin on the same animal was used as a control.

There was no edema observed and erythema was difficult to evaluate because the skin turned black after the treatment. Nevertheless, no signs of irritation were observed. Bayferrox-Schwarz proved not to be irritating.

It was concluded that Bayferrox-Schwarz 350 fluessig was not irritating to the skin.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981-05-12

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The animals were male rabbits, new zealand white. They weighed between 3 and 4 kg and were kept in separate cages at a temperature between 19 and 25oC and a relative humidity between 40 and 60%. The day/night rhytm was 12/12 hours. The animals were fed with a standard diet and were allowed to drink tap water ad libitum.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

Duration of treatment / exposure:

4 hours

Observation period:

one,, 24, 48, 72 hours and 7 days

Number of animals:

3 males

Details on study design:

The skin of three male white rabbits was exposed to 500 mg Bayferrox VP AC 5122. This was applied semi-occlusive to a patch of shaved skin. A second patch of shaved skin was used as a control. Exposure was for 4 hours and after exposure the skin was rinsed with water.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No edema and no erythrema was observed (see Table 1, attachment) after testing of the compound (Fe2O3 83.5 %, FeO 12%, Co 4.5%, so a total iron oxide content of 95.5%). There is no reason to assume that any skin irritating effects would have been diminished by the presence of Co, therefore it is safe to state that this iron oxide does not cause skin irritation.

Other effects:

not observed

Interpretation of results:

GHS criteria not met

Conclusions:

Bayferrox VP AC 5122 M-Investigation of its primary irritation/corrosion on the rabbit skin. The test material is not irritating.
According to the EC-Regulation 1272/2008 and subsequent adaptations, the substance does not require classification as irritating to the skin.

Executive summary:

In a primary dermal irritation study 3 New Zealand white rabbits were dermally exposed to 500 mg of Bayferrox VP AC 5122 M (Fe2O3 83.5 %, FeO 12%, Co 4.5%) in water for 4 hours. Animals then were observed for 7 days. The study was performed according to the OECD Guidelines 404 for acute dermal irritation/corrosion. Bayferrox VP AC 5122 M (Fe2O3 83.5 %, FeO 12%, Co 4.5%) did not cause dermal irritation.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Justification for type of information:

see attachment "Endpoint-specific read-across justification for the iron oxide category" in section 13.

Principles of method if other than guideline:

Sample was applied in the conjunctival sac of one eye. The other eye was used as a control.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data

Vehicle:

unchanged (no vehicle)

Controls:

other: one eye was treated, the other was used as a control

Amount / concentration applied:

50 mg/animal

Duration of treatment / exposure:

no data

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2, one male, one female

Details on study design:

no data

Irritation parameter:

overall irritation score

Remarks on result:

other: no irritation was observed

Irritant / corrosive response data:

not irritating

Other effects:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

Eisenoxid gelb 920 was not irritating.
According to the EC-Regulation 1272/2008 and subsequent adaptations, the substance does not require classification as eye irritant.

Executive summary:

One male and one female New Zealand White Rabbit were exposed to 50 mg FeO(OH) in the conjunctival eye sac of one eye. The other eye served as a control. There was no irritation observed.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

see attachment "Endpoint-specific read-across justification for the iron oxide category" in section 13.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981-05-12

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

3 female rabbits were kept under standard conditions in single cases. The temperature was between 19 and 25°C, the relative humidity was between 40 and 60%. The organisms were fed with a standard diet and were allowed to drink tap water ad libitum.

Vehicle:

other: 0.2% Na-Polyacrylate, 0.1% Preventol D2 and water (remainder)

Controls:

no

Amount / concentration applied:

100 µl was applied

Duration of treatment / exposure:

24 hrs. After 24 hrs the eye was rinsed with a sodium chloride solution.

Observation period (in vivo):

one,, 24, 48, 72 hours and 7 days

Number of animals or in vitro replicates:

3 females

Details on study design:

All three female New Zealand white rabbits were applied 100 µl of the sample in the conjunctival sack of one eye. After application the eye was kept close for about one second. The other eye served as a control. The treated eye was rinsed with physiological salt (NaCl) solution after 24 hrs.
After 1, 24, 48, 72 and 168 hrs the condition of the eye was checked according to OECD guideline 405. Apart from this the eye was checked for swellings, flow of tears and other observable abnormalities.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

no

Other effects:

no

Interpretation of results:

GHS criteria not met

Conclusions:

Bayferrox-Black 350 liquid was not irritating.
According to the EC-Regulation 1272/2008 and subsequent adaptations, the substance does not require classification as eye irritant.

Executive summary:

Three female New Zealand white rabbits were applied 100 µl of undiluted Bayferrox-Schwarz 350 flüssig in the conjunctival sack of one eye. After application the eye was kept close for about one second. The other eye served as a control. The treated eye was rinsed with physiological salt (NaCl) solution after 24 hrs. The condition of the eye was observed 1, 24, 48, 72 and 168 hrs after the application. The condition of the eye was checked according to OECD guideline 405 for cornea, iris, conjunctivea, swelling and excessive tear effects. No sign of any physiological effect of the test material could be observed on the eyes of the treated rabbits at any point in time.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

see attachment "Endpoint-specific read-across justification for the iron oxide category" in section 13.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981-05-12

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Male rabbits were kept under standardised conditions in individual cages at a temperature between 19 and 25°C and a relative humidity between 40 and 60%. The animals weighed between 3 and 4 kg. The day/night rhytm was 12/12 hrs. The animals were fed with a standard diet and were allowed to drink tap water ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 mg fine powdered

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

one,, 24, 48, 72 hours and 7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

Every animal was treated with 100 mg of fine powdered sample in the conjunctival sac of the eye. After application the eye was kept close for 1 second. After 24 hrs the treated eye was rinsed with a physiological salt solution. The other eye was not treated and served as a control.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

not irritating

Other effects:

No exsessive tear formation or any other adverse effects were observed for any animal at any point in time (each animal was evaluated seperately at 1, 24, 48, 72 and 168 h).

Interpretation of results:

GHS criteria not met

Conclusions:

Bayferrox VP AC 5122 M was not irritating.
According to the EC-Regulation 1272/2008 and subsequent adaptations, the substance does not require classification as eye irritant.

Executive summary:

In an eye irritation study, 100 mg of Bayeferrox VP AC 5122 M (a mixture consisting of Fe2O3 83.5 %, FeO 12%, Co 4.5%) was instilled into the conjunctival sac of the eye of 3 rabbits, according to OECD guideline 405. Animals were observed for a total of 168 hrs.  This study showed that Bayeferrox VP AC 5122 M is not eye irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Introductory remark on read-across:

In this dossier, the endpoints skin and eye irritation are not addressed by substance-specific information, but instead based on collected information for all substances of the iron  category. Iron is a transition-metal and is subject at its surface to passivation by the formation of a passive oxide (i. e. iron oxide) coating. In particular for iron metal and granules, the oxide layer will form a quantitatively continuous layer to envelop the entire particle irrespective of product form. In view of this, it may be assumed that human exposure on skin and eye towards iron metal is secondary to that of iron oxide. Thus, unlimited read-across is considered justified. Further information on the read-across approach is given in the report attached to IUCLID section 13.2.

 

Skin irritation

Suberg (1983a) treated three male New Zealand White rabbits in a semi-occlusive patch test with nano sized iron oxide particles Bayferrox VP AC 5122 M (mixture of Fe2O3 83.5 %, FeO 12%, and Co 4.5%, i.e. 95.5% iron oxide (nano-Fe2O3)) according to OECD guideline 404. Rabbits were treated with 0.5 g Bayferrox VP AC 5122 M (Fe2O3) in water  for 4 hours and after exposure skin was rinsed with water. Observations were recorded one, 24, 48, 72 hours and seven days after removal. No dermal irritation in any of the rabbits or clinical signs or body weight loss were observed during the study.

 

Suberg (1984a) treated three male New Zealand White rabbits in a semi-occlusive patch test with Bayferrox-Black 350 liquid (52% Fe3O4) according to OECD guideline 404. Rabbits were treated with 0.5 mL test material in 0.2% Na-Polyacrylate, 0.1% Preventol D2 and water (remainder) for 4 hours and after exposure skin was rinsed with water. Observations were recorded one, 24, 48 and 72 hours as well as seven days after removal. No dermal irritation in any of the rabbits or clinical signs or body weight loss were observed during the study.

 

Mihail (1977) treated one male and one female New Zealand White rabbit on the inner side of the ear with nano sized iron oxide particles yellow Iron Oxide 920 (nano-FeO(OH)). Rabbits were treated with 0.5 g test material for 24 hours and after exposure skin was rinsed and washed with soap and treated with plant oil. Animals were observed for 7 days. Overall, no dermal irritation was observed. Due to insufficient documentation of the study design, the reference was used as supportive information only.

 

 

Conclusion

Based on the findings from two in vivo skin irritation studies with iron oxides (Fe2O3 and Fe3O4) according to OECD 404, it is concluded that iron oxide substances are not considered to be skin irritant.

 

 

Eye irritation

Suberg (1983b) treated three female New Zealand White rabbits in an acute eye irritation study according to OECD guideline 405 with nano sized iron oxide particles Bayferrox VP AC 5122 M (mixture of Fe2O3 83.5 %, FeO 12%, and Co 4.5%, i.e. 95.5% iron oxide (nano-Fe2O3)). One-hundred mg of the test material was placed into the conjunctival sac of the eye. The other eye of each rabbit was not treated and served as a control. The treated eye was rinsed with physiological salt (NaCl) solution after 24 hrs. Observations were recorded one, 24, 48 and 72 hours as well as seven days after administration. Overall, one rabbit showed mild conjunctival redness (score after 24 hours: 1), which was reversible within 48 hours. The remaining rabbits showed no conjunctival redness. No corneal opacity, iritis or conjunctival chemosis were observed in any of the rabbits.

 

Suberg (1984b) treated three New Zealand White female rabbits in an acute eye irritation study according to OECD guideline 405 with Bayferrox-Black 350 liquid (52% Fe3O4). One-hundred µL of the test material in 0.2% Na-Polyacrylate, 0.1% Preventol D2 and water (remainder) was placed into the conjunctival sac of the eye. The other eye of each rabbit was not treated and served as a control. The treated eye was rinsed with physiological salt (NaCl) solution after 24 hrs. Observations were recorded one, 24, 48, 72 hours and seven days after administration. No corneal opacity, iritis, conjunctival redness or conjunctival chemosis were observed in any of the rabbits.

 

Mihail (1977) treated one female and one male New Zealand White rabbit in an acute eye irritation study with nano sized iron oxide particles yellow Iron Oxide 920 (nano-FeO(OH))). Fifty mg of the test material was placed into the conjunctival sac of the eye. The other eye of each rabbit was not treated and served as a control. Animals were observed for 7 days. Overall, no eye irritation was observed. Due to insufficient documentation of the study design, the reference was used as supportive information only.

 

Conclusion

Based on the findings from two in vivo eye irritation studies with iron oxides (Fe2O3 and Fe3O4) according to OECD 405 and a read-across concept, it is concluded that iron oxide substances are not considered to be eye irritant.

Justification for classification or non-classification

Skin irritation

Based on two in vivo skin irritation studies with iron oxides (Suberg 1983a, nano-Fe2O3; Suberg 1984a, Fe3O4) according to OECD guideline 404, iron oxide compounds are not considered to be skin irritants. Therefore, iron and iron oxides should not be classified and labelled for skin irritation according to Regulation (EC) No. 1272/2008.

 

 

Eye irritation

Based on two in vivo eye irritation studies with iron oxides (Suberg 1983b, nano-Fe2O3; Suberg 1984b, Fe3O4) according to OECD guideline 405, iron and iron oxide compounds are not considered to be eye irritants. Therefore, iron oxides should not be classified and labelled for eye irritation according to Regulation (EC) No. 1272/2008.

 

 

Respiratory irritation

The classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. Please refer to the endpoint summaries on acute toxicity (IUCLID endpoint 7.2) and repeated dose toxicity (IUCLID endpoint 7.5) for further information.