Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion:

An experimental study with naphthenic acids, zinc salts is available and do not indicate skin irritating or corrosive potential.

Eye damage:

An experimental study with naphthenic acids, zinc salts is available and do not indicate potential for eye damage.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-12-20 to 2006-01-13
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:
2002-04-24
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
dated 2005-12-13
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quaratier Labaste - F40260 Linxe)
- Weight at study initiation: 2.35 kg - 2.73 kg
- Housing: each animal was kept in an individual box (dimensions: 61 cm X 46 cm X 34 cm) installed in conventional air conditioned animal husbanding.
- Diet (ad libitum): UAR 112 from UAR in 91360 Villemoisson s/Orge, France
- Water (ad libitum): tap-water from public distribution system
- Acclimation period: a minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature: between 18°C and 22°C
- Relative humidity: between 30% and 53%
- Air recycling: at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test item was applied, as supplied, at a dose of 0.5 mL


Duration of treatment / exposure:
4 hours
Observation period:
1 hour and then 24, 48 and 72 hours as well as 4 to 14 days after removal of the patch
Number of animals:
3 male rabbits
Details on study design:
Initially, a single animal was treated. After consideration of cutaneous responses produced in the first treated animal, two additional animals were treated.
TEST SITE
- Area of exposure: approximately 24 hours before the test, the rabbits' backs and flanks are shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm^2. Any animal with skin lesions is replaced.
The test product is applied to a small area (approx. 6 cm^2) of shorn skin (unaffected zone) and covered with a gauze patch, which is maintained in position by a semi-occlusive dressing. The dressing is covered with an elastic strap taped in place around the animal's body, taking care not to impede its respiratory and abdominal movements.

SCORING SYSTEM: according to Draize scale

OBSERVATIONS:
The systemic toxicity, expressing by behavioural abnormalities, alteration of neuro-vegetative reactions or decrease feeding, and any toxic effects are to be logged and described.
The animals are weighed at the start and at the end of the test.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight dryness from D2 to D14
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:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
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:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight dryness from D3 to D9
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
One hour after the test item application, very slight (barely perceptible) erythema was noted.
Twenty four hours after the test item application, it was noted, on the treated area, a very slight to well-definite erythema in the 3 animals. Moreover, it was noted a slight dryness on the cutaneous treated area, from the 2nd or 3rd day of the test in two animals. This reaction was ever noted at the end of the observation time (D14) in one animal.
Interpretation of results:
not irritating
Conclusions:
The test substance is not irritating to the skin.
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as skin irritant.
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because they hydrolyse to common products.

This prediction is supported by toxicological data on the substances themselves and on the dissolution products of the substances.
Target and source substances are mono-constituent substances. Both substances differ only in the production process, resulting in (i) an neutral product and (ii) a basic product.

The target substance is the basic product containing a slightly higher zinc content. The dissolution product, namely the zinc cation, is not the driver for toxic effects.
Consequently, the target substance is identical to the source substance and share a structural similarity with common functional groups, carboxylic acid, alkyl side chains.

Therefore, read-across from the existing skin and eye irritation studies on the source substance is considered as an appropriate adaption to the standard information requirements of Annex VII and VIII, 8.1 and 8.2 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

The justification of the proposed read-across approach is elaborated in the next chapters. Please find this information in the attachements as well.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
a) Target substance
The target substance naphthenic acids, zinc salts, basic is a mono-constituent substance (EC: 282-762-6, CAS: 84418-50-8).
b) Source substance
The source substance naphthenic acids, zinc salts is a mono-constituent substance (EC: 234-409-2, CAS: 12001-85-3).
c) Purity and impurities
The source substance is derived from the same educts in the production process. Consequently, the hazard profile of the target substance is intrinsically covered.


3. ANALOGUE APPROACH JUSTIFICATION
a) Structural similarity and functional groups
The structure of the target and source substances are the same, namely a naphthenic acids, zinc salt. The target substance is the basic product containing a slightly higher zinc content compared to the neutral product. The dissolution product, namely the zinc cation, is not the driver for toxic effects with regard to Human Health and especially to local effects.

b) Common breakdown products
The common characteristic of the target substance and the source substance is that both liberate the same moiety upon dissolution in aqueous media. Zinc cations and naphthenate anions are formed upon dissolution under toxicological relevant conditions such as body fluids and in the environment.


4. DATA MATRIX
A comparison of the experimental toxicological data between the source and target substance is not applicable in the applied approach, since the overall ecotoxicity/systemic toxicity of the target substance is assessed by taking the (eco-)toxicological profile of the zinc cation and the acid anion (naphthenic acid) into account. An endpoint-specific description is provided in the respective endpoint summaries of both assessment entities.
The structural similarities between the source and the target substances and the similarities in their breakdown products presented above support the read-across hypothesis. Adequate, reliable and available scientific information indicates that the source and target substances and their subsequent degradation product have similar toxicity profiles.

Based on the considerations above, it can be concluded that the results of the skin and eye irritation studies conducted with the source substance is likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirements of Annex VII and VIII, 8.1 and 8.2
Since the source substance is not classified for skin or eye irritation, the target substance naphthenic acids, zinc salts, basic will not be classified as well. Thus, the information requirements of Annex VII and VIII, 8.1 and 8.2. are fulfilled by the source and target substance.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
no
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight dryness from D2 to D14
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:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
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:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight dryness from D3 to D9
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
One hour after the test item application, very slight (barely perceptible) erythema was noted.
Twenty four hours after the test item application, it was noted, on the treated area, a very slight to well-definite erythema in the 3 animals. Moreover, it was noted a slight dryness on the cutaneous treated area, from the 2nd or 3rd day of the test in two animals. This reaction was ever noted at the end of the observation time (D14) in one animal.
Interpretation of results:
not irritating
Conclusions:
The test substance is not irritating to the skin.
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as skin irritant.
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
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-01-02 to 2006-01-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
dated 2005-12-13
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quaratier Labaste - F40260 Linxe)
- Weight at study initiation: 2.42 kg - 2.61 kg
- Housing: each animal was kept in an individual box (dimensions: 61 cm X 46 cm X 34 cm) installed in conventional air conditioned animal husbanding.
- Diet (ad libitum): UAR 112 from UAR in 91360 Villemoisson s/Orge, France
- Water (ad libitum): tap-water from public distribution system
- Acclimation period: a minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature: between 20°C and 22°C
- Relative humidity: between 35% and 44%
- Air recycling: at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a volume of 0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye, the other eye remained untreated serving as control.


Duration of treatment / exposure:
not applicable
Observation period (in vivo):
1 hour, 24, 48 and 72 hours as well as 4 days following treatment
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Both eyes of each experimental animal provisionally selected for testing should be examined before testing starts. Animals showing eye irritation, ocular defects, or pre-existing corneal injury should not be used.

SCORING SYSTEM: according to Draize scale
Any other lesions in the eye (e.g. pannus, staining) or adverse systemic effects should also be reported

TOOL USED TO ASSESS SCORE: examinations of reactions can be facilitated by use of a binocular loupe, had slit-lamp, biomicroscope or other suitable device. After recording the observations at 24 hours, the eyes may be further examined with the aid of fluorecein.

OBSERVATIONS: the systemic toxicity, expressing by behavioural abnormalities, alteration of neuro-vegetative reactions or decrease feeding, and any toxic effects are to be logged and described.
The animals are weighed at the start and at the end of the test.
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:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
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:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
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:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 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:
It was only recorded slightly conjunctivae reactions, similar in the 3 animals and rapidly reversible: a slight redness noted 1 hour after the test item instillation and totally reversible between 4th and the 5th day of the test associated with a slight chemosis noted 1 hour after the test item instillation and totally reversible between 2nd and the 3rd day.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material is not irritating to the eye.
According to the EC Regulation No. 1272/2008 and its subsequent Amendments, the test substance is not classified as eye irritant.
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because they hydrolyse to common products.

This prediction is supported by toxicological data on the substances themselves and on the dissolution products of the substances.
Target and source substances are mono-constituent substances. Both substances differ only in the production process, resulting in (i) an neutral product and (ii) a basic product.

The target substance is the basic product containing a slightly higher zinc content. The dissolution product, namely the zinc cation, is not the driver for toxic effects.
Consequently, the target substance is identical to the source substance and share a structural similarity with common functional groups, carboxylic acid, alkyl side chains.

Therefore, read-across from the existing skin and eye irritation studies on the source substance is considered as an appropriate adaption to the standard information requirements of Annex VII and VIII, 8.1 and 8.2 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

The justification of the proposed read-across approach is elaborated in the next chapters. Please find this information in the attachements as well.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
a) Target substance
The target substance naphthenic acids, zinc salts, basic is a mono-constituent substance (EC: 282-762-6, CAS: 84418-50-8).
b) Source substance
The source substance naphthenic acids, zinc salts is a mono-constituent substance (EC: 234-409-2, CAS: 12001-85-3).
c) Purity and impurities
The source substance is derived from the same educts in the production process. Consequently, the hazard profile of the target substance is intrinsically covered.


3. ANALOGUE APPROACH JUSTIFICATION
a) Structural similarity and functional groups
The structure of the target and source substances are the same, namely a naphthenic acids, zinc salt. The target substance is the basic product containing a slightly higher zinc content compared to the neutral product. The dissolution product, namely the zinc cation, is not the driver for toxic effects with regard to Human Health and especially to local effects.

b) Common breakdown products
The common characteristic of the target substance and the source substance is that both liberate the same moiety upon dissolution in aqueous media. Zinc cations and naphthenate anions are formed upon dissolution under toxicological relevant conditions such as body fluids and in the environment.


4. DATA MATRIX
A comparison of the experimental toxicological data between the source and target substance is not applicable in the applied approach, since the overall ecotoxicity/systemic toxicity of the target substance is assessed by taking the (eco-)toxicological profile of the zinc cation and the acid anion (naphthenic acid) into account. An endpoint-specific description is provided in the respective endpoint summaries of both assessment entities.
The structural similarities between the source and the target substances and the similarities in their breakdown products presented above support the read-across hypothesis. Adequate, reliable and available scientific information indicates that the source and target substances and their subsequent degradation product have similar toxicity profiles.

Based on the considerations above, it can be concluded that the results of the skin and eye irritation studies conducted with the source substance is likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirements of Annex VII and VIII, 8.1 and 8.2
Since the source substance is not classified for skin or eye irritation, the target substance naphthenic acids, zinc salts, basic will not be classified as well. Thus, the information requirements of Annex VII and VIII, 8.1 and 8.2. are fulfilled by the source and target substance.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
no
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:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
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:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
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:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 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:
It was only recorded slightly conjunctivae reactions, similar in the 3 animals and rapidly reversible: a slight redness noted 1 hour after the test item instillation and totally reversible between 4th and the 5th day of the test associated with a slight chemosis noted 1 hour after the test item instillation and totally reversible between 2nd and the 3rd day.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material is not irritating to the eye.
According to the EC Regulation No. 1272/2008 and its subsequent Amendments, the test substance is not classified as eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

One reliable in vivo study described by Richeux (2006) (OECD 404; GLP compliant), conducted with naphthenic acids, zinc salts, is considered to be reliable without restrictions. The skin irritation was scored according to the Draize scale. The mean score (24, 48, 72 h) for erythema and oedema for all three animals were as follows:

Erythema: 1, 0.67 and 0.67

Oedema: 0 (all animals)

Furthermore, it was noted a slight dryness on the cutaneous treated area, from the 2nd or 3rd day of the test in two animals. This reaction was ever noted at the end of the observation time (D14) in one animal.

Unlimited read-across from naphthenic acids, zinc salts to naphthenic acids, zinc salts, basic is justified, since the overbased naphthenic acids, zinc salts, basic only contains a surplus of zinc, which is, however, known not to be the driver for toxic effects with regard to Human Health and especially to local effects.

According to regulation (EC) 1272/2008 and its subsequent amendments the substance is not to be classified as skin irritant.

Eye irritation

One reliable in vivo study described by Richeux (2006) (OECD 405; GLP compliant), conducted with naphthenic acids, zinc salts, is considered to be reliable without restrictions. The eye irritation was scored according to the Draize scale. The mean score (24, 48, 72 h) for cornea, iris conjunctivae redness and chemosis all three animals were as follows:

Cornea: 0 (all animals)

Iris: 0 (all animals)

Conjunctivae redness: 1, 0.67 and 0.67

Chemosis: 0.33, 0 and 0

The study was terminated after 4 days.

Unlimited read-across from naphthenic acids, zinc salts to naphthenic acids, zinc salts, basic is justified, since the overbased naphthenic acids, zinc salts, basic only contains a surplus of zinc, which is, however, known not to be the driver for toxic effects with regard to Human Health and especially to local effects.

According to regulation (EC) 1272/2008 and its subsequent amendments the substance is not to be classified as eye irritant

Justification for classification or non-classification

According to experimental studies conducted with naphthenic acids, zinc salts, no potential for skin and eye irritation/corrosion could be observed.

According to the criteria of regulation (EC) 1272/2008 and its subsequent amendments, naphthenic acids, zinc salts, basic does not have to be classified and has no obligatory labelling requirement for skin, eye or respiratory irritation.