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Registration Dossier
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EC number: 941-718-2 | CAS number: -
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 22 July - 21 August 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- 1. Hypothesis for the analogue approach:
The hypothesis for the analogue approach is that both the registration substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics (target substance), and the test substances, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (source substance) are produced from the same Fischer-Tropsch substance, GTL Gasoil, by fractional distillation. The substances are C9-C14 Aliphatics [≤2% Aromatics] Hydrocarbon Solvents.
The source substances contain the all of the constituents of the target substance. The substances have constituents that are part of the same homologous series and have many constituents in common. The substances therefore have qualitatively similar properties (RAAF Scenario 2 applies).
2. Source and target chemical(s)
The source substance Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics is composed of linear, branched and cyclic hydrocarbons of chain length C8-C11
The target substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics, is composed of linear, branched and cyclic hydrocarbons of chain length C9-C11.
3. Analogue approach justification
The constituents of the source and target substances are all hydrocarbons. Identical constituents have identical toxicological properties. The source substances cover the full carbon chain length of the target substance.
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- skin irritation: in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 22 July - 21 August 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- 1. Hypothesis for the analogue approach:
The hypothesis for the analogue approach is that both the registration substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics (target substance), and the test substances, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (source substance) are produced from the same Fischer-Tropsch substance, GTL Gasoil, by fractional distillation. The substances are C9-C14 Aliphatics [≤2% Aromatics] Hydrocarbon Solvents.
The source substances contain the all of the constituents of the target substance. The substances have constituents that are part of the same homologous series and have many constituents in common. The substances therefore have qualitatively similar properties (RAAF Scenario 2 applies).
2. Source and target chemical(s)
The source substance Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics is composed of linear, branched and cyclic hydrocarbons of chain length C8-C11
The target substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics, is composed of linear, branched and cyclic hydrocarbons of chain length C9-C11.
3. Analogue approach justification
The constituents of the source and target substances are all hydrocarbons. Identical constituents have identical toxicological properties. The source substances cover the full carbon chain length of the target substance. - Reason / purpose for cross-reference:
- read-across source
- Irritation parameter:
- erythema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 Days
- Remarks on result:
- positive indication of irritation
- Remarks:
- Bald skin and/or scaliness found at 14 Days after administration
- Irritation parameter:
- erythema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- positive indication of irritation
- Remarks:
- bald skin on application site
- Irritation parameter:
- erythema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- positive indication of irritation
- Remarks:
- scaliness and bald skin on application side
- Irritation parameter:
- edema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- edema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- probability of mild irritation
- Irritation parameter:
- edema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- Irritation: An exposure period of three minutes to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in very slight erythema and very slight oedema in the treated skin area of the rabbit. One hour of exposure resulted in well-defined erythema and very slight oedema. Furthermore, the animal showed very superficial fissuring of the skin, bald skin and/or scaliness 7 and 14 Days after exposure. Four hours exposure to 0.5 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 Days after exposure).
Corrosion: There was no evidence of a corrosive effect on the skin. - Other effects:
- Coloration/remnants: No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
Toxicity/mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- An in vivo skin irritation study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 404 and in compliance with GLP (WIL Research, 2014b). Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure). On the basis of these results, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics were concluded to be irritating to skin..
- Executive summary:
This data is being read across from the source study that tested Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics based on analogue read across.
Primary skin irritation/corrosion study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics in the rabbit (semi-occlusive application).
The study was carried out based on the guidelines described in:
OECD No.404 (2002); "Acute Toxicity - Skin irritation"
EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion"
US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation
JMAFF Guidelines (2000), including the most recent revisions.
Initially, one rabbit was exposed to three samples of 0.5 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily for 4 days after treatment and 7 and 14 days after exposure. Based on the absence of severe skin reactions, two further animals exposed for 4 hours to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics at a later stage.
Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 Days after exposure).
Based on the 24-72 hours mean erythema score of 2.3 in two animals and persisting skin reactions and according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) (including all amendments), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics should be classified as : skin irritant (Category 2).
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures(including all amendments), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics should be classified as Irritant (Category 2) and labeled as H315: Causes skin irritation.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics
- EC Number:
- 940-733-1
- Molecular formula:
- C8H18 to C11H24
- IUPAC Name:
- Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics
- Test material form:
- other: Clear colourless liquid
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- - Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used withihn the study were between 12 and 24 weeks old.
- Weight at study initiation: Body weights were at least 1.5 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.
IN-LIFE DATES: From: 22 July - 21 August 2014
Test system
- Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: Adjacent areas of the untreated skin of each animal served as controls.
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.5 mL - Duration of treatment / exposure:
- Single application.
- Observation period:
- 14 days.
- Number of animals:
- 3 males.
- Details on study design:
- STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of skin irritation observed in the first animal.
TEST SUBSTANCE PREPARATION
The test substance was applied undiluted as delivered by the sponsor.
TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
The test substance was applied to the skin of one flank, using a patch of 2x3 cm.
REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.
OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: In the initially treated animal, the skin reactions of all visible treated sites were assessed immediately after removal of a dressing and approximately 1, 24, 48, 72 hours after the removal of the last dressing and test substance. After the 4 hours exposure in two further animals, the skin reactions were assessed approximately 1, 24, 48, 72 hours after the removal of the dressing and test substance. For the duration of the skin reactions, further observations were made 7 and 14 (maximum) days after exposure. Readings were done under true light using Philips Master TL-5 HO 49 watt/840 lamps. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of each animal serve as controls.
SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- erythema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 Days
- Remarks on result:
- positive indication of irritation
- Remarks:
- Bald skin and/or scaliness found at 14 Days after administration
- Irritation parameter:
- erythema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- positive indication of irritation
- Remarks:
- bald skin on application site
- Irritation parameter:
- erythema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- positive indication of irritation
- Remarks:
- scaliness and bald skin on application side
- Irritation parameter:
- edema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 14 days
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- edema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- probability of mild irritation
- Irritation parameter:
- edema score
- Remarks:
- 4-hour treatment
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- Irritation: An exposure period of three minutes to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in very slight erythema and very slight oedema in the treated skin area of the rabbit. One hour of exposure resulted in well-defined erythema and very slight oedema. Furthermore, the animal showed very superficial fissuring of the skin, bald skin and/or scaliness 7 and 14 Days after exposure. Four hours exposure to 0.5 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 Days after exposure).
Corrosion: There was no evidence of a corrosive effect on the skin. - Other effects:
- Coloration/remnants: No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
Toxicity/mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Applicant's summary and conclusion
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- An in vivo skin irritation study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 404 and in compliance with GLP (WIL Research, 2014b). Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure). On the basis of these results, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics were concluded to be irritating to skin..
- Executive summary:
Primary skin irritation/corrosion study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics in the rabbit (semi-occlusive application).
The study was carried out based on the guidelines described in:
OECD No.404 (2002); "Acute Toxicity - Skin irritation"
EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion"
US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation
JMAFF Guidelines (2000), including the most recent revisions.
Initially, one rabbit was exposed to three samples of 0.5 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily for 4 days after treatment and 7 and 14 days after exposure. Based on the absence of severe skin reactions, two further animals exposed for 4 hours to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics at a later stage.
Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 Days after exposure).
Based on the 24-72 hours mean erythema score of 2.3 in two animals and persisting skin reactions and according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) (including all amendments), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics should be classified as : skin irritant (Category 2).
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures(including all amendments), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics should be classified as Irritant (Category 2) and labeled as H315: Causes skin irritation.
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