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Administrative data

Description of key information

skin irritation (OECD 404): not irritating
eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
limited documentation
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand Albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Robinson Services Inc. (Clemmons, NC, USA)
- Diet (e.g. ad libitum): free access to lab chow (Purina Rabbit Chow No. 5326, St. Louis, Mo, USA)
- Water (e.g. ad libitum): municipal water ad libitum
- Acclimation period: 9 days prior to initiation of dosing


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 24 °C
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: corn oil
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/pad of the 70% mixture
- Concentration (if solution): 70% w/w mixture of niacin-bound chromium III in corn oil
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after removal of test substance
Number of animals:
one male, two nulliparous and non-pregnant females
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- % coverage: 100
- Type of wrap if used: 4-ply gauze pad; pad and entire trunk of animal secured with semi-occlusive 3 in. Micropore tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle cleaning of any residual test substance
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize Scoring System and calculation of Primary dermal irritation index
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
1 male, 2 female
Score:
0.5
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
1
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
1 h after the application, very-slight erythema was observed at all three treated sites. The overall incidence and severity of irritation decreased with time. All animals were free from dermal irritation within 48 h.
Other effects:
Apart from the dermal irritation noted, all animals appeared active and healthy and with no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Table: Primary dermal irritation scores in male and female New Zealand albino rabbitsaafter exposure to niacin-bound chromium

Time post installation (h)

Incidence of dermal irritation

Total PDIb

Primary Dermal Irritation Index (PDII)

erythema

edema

Individual

1

1.0

0.0

1.0

0.5

24

1.0

0.0

1.0

48

0.0

0.0

0.0

72

0.0

0.0

0.0

(a) Average values (n=3), (b) primary dermal irritation = average erythema + avergae edema

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with limited documentation
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Remarks:
reporting in publication not as detailed as in a guideline study report
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Robinson Services Inc. (Clemmons, NC, USA)
- Diet (e.g. ad libitum): free access to lab chow (Purina Rabbit Chow No. 5326, St. Louis, Mo, USA)
- Water (e.g. ad libitum): municipal water ad libitum
- Acclimation period: 7 days prior to initiation of dosing


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
water
Controls:
other: left eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (0.05 g) of NBC in water
Duration of treatment / exposure:
Application into the conjuntival sac lasted for appr. 1 sec. The test substance remained in the eye.
Observation period (in vivo):
1, 24, 48, and 72 h post-installation
Number of animals or in vitro replicates:
two males, one nulliparous and non-pregnant female
Details on study design:
SCORING SYSTEM: primary eye irritation score according to system by Kay and Calandra 1962; eye lesions were scored were scored according to Draize scale


TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Max. score:
2
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 h
Score:
0
Irritation parameter:
other: conjunctivitis incidence
Basis:
other: per three animals
Time point:
other: 1 h
Score:
3
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
No corneal opacity or iritis was observed in any treated eye during the study. One hour following test substance instillation, all treated eyes exhibited conjunctivitis. All animals were free of ocular irritation within 24 h.
Other effects:
Apart from the eye irritation noted, all animals appeared active and healthy. There were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Under the conditions of this study niacin-bound chromium is practically non-irritating to the eye.

Table: Incidence, severity and reversibility of ocular irritation in New Zealand albino rabbits after exposure to niacin-boun chromium (n=3)

Time post installation (h)

Incidence of ocular irritation

Severity of irritation

Corneal opacity

Iritis

Conjunctivitis

MMT(a) score

1

0/3

0/3

3/3

2.0

24

0/0

0/0

0/0

0.0

48

0/0

0/0

0/0

0.0

72

0/0

0/0

0/0

0.0

(a) MMT = maximum mean total

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

The read-across substance Niacin bound Chromium (ChromeMate CM-100M) was investigated in an acute dermal irritation study performed equivalent to OECD 404 and GLP (Shara, 2005). The test substance dissolved in corn oil was applied to the shaved skin of one male and two New Zealand Albino rabbits under semiocclusive conditions for 4 hours. 1 h after the application, very-slight erythema was observed at all three treated sites. The overall incidence and severity of irritation decreased with time. All animals were free from dermal irritation within 48 h. Apart from the dermal irritation noted, all animals appeared active and healthy and with no other signs of gross toxicity. Therefore, the source substance was considered to be not irritating to the skin under the conditions of this test. In addition, an acute dermal toxicity study performed with the target substance Acetic acid, chromium salt, basic does not indicate skin irritation up to the limit dose level of 2000 mg/kg body weight (Seguier, 2008).

Eye irritation/corrosion

A HET-CAM was performed with the target substance Acetic acid, chromium salt, basic which revealed no corrosive effects (Paulus and Rudolf, 2008).

In addition, the read-across substance Niacin bound Chromium (ChromeMate CM-100M) was investigated in an acute eye irritation study performed equivalent to OECD 405 and GLP (Shara, 2005). 0.1 mL of the substance dissolved in water was applied to the conjuctival sac of one 1 male and two female rabbits. The untreated eye served as control. The eyes were investigated 1, 24, 48, and 72 h post-installation. No corneal opacity or iritis was observed in any treated eye during the study. One hour following test substance instillation, all treated eyes exhibited conjunctivitis. All animals were free of ocular irritation within 24 h. Apart from the eye irritation noted, all animals appeared active and healthy and with no other signs of gross toxicity. Therefore, the source substance was considered to be not irritating to the eye under the conditions of this test.


Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on the skin and eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.