Registration Dossier

Administrative data

Description of key information

Two studies on skin irritation potential are presented on structurally related substances as valid read across candidates: 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1 (OECD 404) and Iron(2+) dicyclopenta-2,4-dienide (Ferrocene), CAS Number 102-54-5, EC Number 203-039-3 (comparable to OECD 404).

In an OECD 404 study, 1,1'-Bis(ferrocenyl)octane was found to be not irritating to skin, the GHS criteria were not met.

In the case of iron (2 +) dicyclopenta-2,4 -dienide (ferrocene), CAS Number 102 -54 -5, EC Number 203 -039 -3, the skin irritation potential was investigated in a study which was comparable to to guideline OECD 404. Iron (2 +) dicyclopenta-2,4 -dienide (ferrocene) was found to be not irritating to skin, the GHS criteria were not met.

As regards eye irritation two studies on skin irritation potential are presented on structurally related substances as valid read across candidates: 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1 (OECD 404) and Iron(2+) dicyclopenta-2,4-dienide (Ferrocene), CAS Number 102-54-5, EC Number 203-039-3 (comparable to OECD 404).

In an OECD 405 study, 1,1'-Bis(ferrocenyl)octane was found not to be irritating to eyes, the GHS criteria were not met.

In the case of iron (2 +) dicyclopenta-2,4 -dienide (ferrocene), CAS Number 102 -54 -5, EC Number 203 -039 -3, the eye irritation potential was investigated in a study which was comparable to to guideline OECD 404. Iron (2 +) dicyclopenta-2,4 -dienide (ferrocene) was found to be not irritating to eyes, the GHS criteria were not met.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo study available, ex NONS; OECD 404
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Read across data is presented from the structurally related substance, 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1. This substance bears a close similarity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0, the distinction being that the alkyl bridging functionality between the two ferrocene moieties is an octyl derivative as opposed to an isopropyl derivative.
Source species:
rabbit
Source strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Control samples:
yes, concurrent no treatment
Amount/concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
1 h, 24 h, 48 h, 72 h, 7 d, 14 d
Number of animals:
3
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 3 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0.66
Reversibility:
fully reversible within: 3 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0.33
Reversibility:
fully reversible within: 3 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 3 days.
Other effects:
No effects on mean body weight and body weight development were noted. During the study the behaviour and general state of animals were normal.
Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404, 1,1'-Bis(ferrocenyl)octane is slightly irritating to skin. It is not classifed for skin irritant according to GHS criteria.
Executive summary:

The skin irritation/corrosion potential of 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1was investigated in accordance with the standardised guideline OECD 404.

An OECD 404 study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results was performed on 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1.

The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

This substance is considered to be sufficiently close in structural integrity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0 so as to justify valid read across.

Under the conditions of the study 1,1'-Bis(ferrocenyl)octane is slightly irritating to skin. It is not classifed for skin irritant according to GHS criteria.

Endpoint:
skin irritation / corrosion, other
Remarks:
OECD 404
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Specific details on test material used for the study:
Read across data is presented from the structurally related substance, iron(2+) dicyclopenta-2,4-dienide (ferrocene), CAS Number 102-54-5, EC Number 203-039-3. This substance bears a close similarity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0. Therefore, it is considered that read-across is valid.
Species:
rabbit
Strain:
other: White Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: dr. Karl.Thomae GmbH, Biberach
- Weight at study initiation: 2.1-2.8kg
- Diet:ad libitum
- Water: ad libitum
- Acclimation period: 14days
- Sex: male

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-1
- Humidity (%): 60+-5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours then patch removed.
Observation period:
3 days
Number of animals:
3
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
72 h
Score:
0.5
Max. score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0.56
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Interpretation of results:
GHS criteria not met
Conclusions:
In a Study performed comparable to OECD Guideline 404, Ferrocene on the skin of male rabbits is a non-irritant. This is based on the primary dermal irritation index value of 0.5. GHS criteria are not met.
Executive summary:

The skin irritation potential of iron(2+) dicyclopenta-2,4-dienide (ferrocene), CAS Number 102-54-5, EC Number 203-039-3 was investigated in a study which was comparable to guideline OECD 404.

The study was assigned a reliability score of 2 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

This substance is considered to be sufficiently close in structural integrity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0 so as to justify valid read across.

In this study, ferrocene on the skin of male rabbits is a non-irritant.   This is based on the primary dermal irritation index value of 0.5. GHS criteria are not met.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Remarks:
Ex NONS.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 2004 to June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Read across data is presented from the structurally related substance, 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1. This substance bears a close similarity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0, the distinction being that the alkyl bridging functionality between the two ferrocene moieties is an octyl derivative as opposed to an isopropyl derivative.
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml
Number of animals or in vitro replicates:
3
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
1.33
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(mean score)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 3 days.
Other effects:
No effects on mean body weight and body weight development were noted. During the study the behaviour and general state of animals were normal.
Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405, 1,1'-Bis(ferrocenyl)octan is slightly irritating to the eyes. It is not classified for eye irritation. GHS criteria are not met.
Executive summary:

The eye irritation potential of1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1was investigated in accordance with the standardised guideline OECD 405.

An OECD 405 study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results was performed on 1,1'-Bis(ferrocenyl)octane, CAS Number 501410-94-2, EC Number 479-710-1.

The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

This substance is considered to be sufficiently close in structural integrity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0 so as to justify valid read across.

Under the conditions of the study 1,1'-Bis(ferrocenyl)octane is not irritating to eyes. It is not classifed for eye irritation according to GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Specific details on test material used for the study:
Read across data is presented from the structurally related substance, iron(2+) dicyclopenta-2,4-dienide (ferrocene), CAS Number 102-54-5, EC Number 203-039-3. This substance bears a close similarity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0. Therefore, it is considered that read-across is valid.
Species:
rabbit
Strain:
other: White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr Karl Thomae, GmbH, Biberach
- Weight at study initiation: 2.2-2.4kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-1
- Humidity (%): 60+-5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
6 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
not measured/tested

Conjunctiva effects are probably due to physical powder irritation. These effects are reversible within 24 hours.

Interpretation of results:
GHS criteria not met
Conclusions:
In a Study performed to OECD Guideline 405, Ferrocene was non-irritating for the eye and ocular mucosa. of a rabbit. This is based on the overall score of (2.5/100) = 0.02. GHS criteria are not met.
Executive summary:

The eye irritation potential of iron(2+) dicyclopenta-2,4-dienide (ferrocene), CAS Number 102-54-5, EC Number 203-039-3 was investigated in a study which was comparable to guideline OECD 405.

The study was assigned a reliability score of 2 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

This substance is considered to be sufficiently close in structural integrity to 1,1''-isopropylidenediferrocene, CAS Number 12609-95-9, EC Number 235-719-0 so as to justify valid read across.

In this study, ferrocene in the eye of male rabbits is a non-irritant.   This is based on the overall score of (2.5/110) = 0.02. GHS criteria are not met.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification


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