Registration Dossier

Administrative data

Description of key information

Skin irritation: In vitro: Not irritating (renewable hydrocarbons of wood origin (diesel type fraction))
In vivo: Irritating (read-across substance; Fuel oil, no.2 i.e. #2 Home Heating Oil (50% cat))
Eye irritation: In vitro: Not irritating (renewable hydrocarbons of wood origin (diesel type fraction))
In vivo: Not irritating (read-across substance; Fuel oil, no.2 i.e. #2 Home Heating Oil (50% cat))

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:
weight of evidence
Study period:
1979-04-30 to 1979-05-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is classified as reliable with restrictions because it is an acceptable and a well-documented study report, but is done for the read-across substance. Read-across justification: Based on the chemical composition, the renewable hydrocarbons produced from raw materials such as fatty acid rich oil like Crude Tall Oil (CTO) or triglyserides, using a hydrotreatment process have similar hydrocarbon fractions and they contain the same critical constituents than fossil diesel fuels. According to the identified hydrocarbon blocks, the typical carbon number ranges and the physicochemical properties, the renewable hydrocarbons with diesel type fractions can be considered as having structural similarities and similar behaviour in contact with water and in the physiological processes than the analogue source substances (fossil diesel fuels). Their irritation properties, skin sensitisation property as well as acute and long-term adverse effects to human health is similar. Therefore, and in order to avoid the unnecessary animal testing, the read-across data from the analogue fossil diesel fuels is used to evaluate skin and eye irritation, the genetic toxicity, carcinogenicity, developmental toxicity and short term and/or long-term toxicological effects of the target substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
24 hours exposure
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Pel-Freeze Farms, Inc.
- Age at study initiation: 4 months
- Weight at study initiation: 2 to 4 kilograms
- Housing: housed individually in stainless steel cages with grated bottoms
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
Animals were observed at 24 and 72 hours and 7 and 14 days
Number of animals:
three males and three females
Details on study design:
TEST SITE
- Area of exposure: four test sites located lateral to the midline of the back (two sites on each side)
- % coverage: not reported
- Type of wrap if used: Saran Wrap, Band-Aid, and Conform elastic tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess test material was wiped off the skin with dampened gauze sponges
- Time after start of exposure: 24 hours

SCORING SYSTEM: scored using the Draize technique
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2.5
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: intact skin
Irritant / corrosive response data:
Both erythema and oedema were observed at the 24 hour, 72 hour, and 7 day recording periods. By day 14 no signs of oedema and erythema were observed.
Other effects:
During the 14 day observation period hair did not regrow on the test sites, but grew normally on the surrounding skin.

Table 1: Average dermal irritation scores

 

24 hours

72 hours

7 days

14 days

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Abraded

1.58

0.75

3.08

1.92

2.75

1.50

0

0

Intact

1.58

0.83

3.42

2.17

2.75

1.42

0

0

Primary Irritation Score: 3.83

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
New Zealand White rabbits were exposed to the read-across substance, similar to renewable hydrocarbons of wood origin (diesel type fraction), for 24 hours in occlusive conditions. The mean erythema and oedema scores during the 24 to 72 hour observation periods were 2.5 and 1.5, respectively. Based on the conditions of this study, the test substance is considered an skin irritant.
Executive summary:

This skin irritation study was conducted for the read-across substance, #2 Home Heating Oil (50% cat]), similar to the registering substance.

In this study New Zealand White rabbits (3/sex) were exposed to 0.5 mL of test substance applied to four shaved test area on the back (2 abraded and 2 intact) via a a gauze patch. Gauze patches were secured with Saran wrap and Band-Aids and wrapped with Conform elastic tape. After 24 hours of exposure the covering were removed and the test sites were wiped with gauze sponges to removed excess material. Animals were observed at 24 hours, 72 hours, 7 and 14 days post-administration. Signs of erythema and eodema were scored according to the draize technique.

Signs of erythema and oedema were evident at 24 hours, 72 hours, and 7 days. By day 14 all erythema and oedema had subsided. The mean erythema and oedema scores during the 24 to 72 hour observation periods were 2.5 and 1.5, respectively. Based on the conditions of this study, the test material is classified as an irritant.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it is an acceptable and a well-documented study report, but is conducted for the read-across substance.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Weight of evidence approach was used to evaluate the testing needs of this endpoint. There is available reliable guideline in vitro skin irritation study conducted for the substance (Warren, 2012). Further evidence on skin irritation is also derived from the in vivo skin irritation data obtained from read-across substance (API, 1980a).

In vitro skin irritation study was carried out based on the OECD 439 guideline and in compliance with OECD principles of Good Laboratory Practice (GLP) (Warren, N., 2012). The test was used to evaluate the skin irritation potential of the substance using EPISKIN TM reconstituted human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours. The principle of assay was based on the cytotoxicity in human epidermal cultures following topical exposure of the test item by means of colourimetric MTT reduction assay. The relative mean viability of the test item treated tissues was 95.3% after a 15 min exposure period. Based on this value renewable hydrocarbons of wood origin (diesel type fraction) was considered to be non-irritant to the skin.

This UVCB substance is a complex mixture of hydrocarbons. When there is no data on the substance itself the read-across data was also used to avoid unnecessary animal testing. The read-across from fossil diesel fuels is justified because the toxicokinetics and toxicological properties of renewable diesel are considered similar to fossil diesel fuels based on the similar composition and physical-chemical properties. The read-across justification and the data matrices are presented in the annex 1 of the CSR.

The in vivo skin irritation potential is evaluated from published data available from read-across fossil diesel fuel. API (1980a) had conducted in vivo skin irritation study for the similar substance, Fuel oio, no.2 i.e. #2 Home Heating Oil (50% cat). In this study New Zealand White rabbits were exposed to #2 Home Heating Oil (50% cat) for 24 hours in occlusive conditions. The mean erythema and oedema scores during the 24 to 72 hour observation periods were 2.5 and 1.5, respectively. According to the conditions of this study, the test substance is considered a skin irritant.

Based on the in vivo skin irritation study result conducted for the read-across substance renewable hydrocarbons of wood origin (diesel type fraction) will be classified for skin irritation.

Eye irritation

Weight of evidence approach was used to evaluate the testing needs of this endpoint. Reliable in vitro eye irritation study was conducted for renewable hydrocarbons of wood origin (diesel type fraction) (Warren, N., 2012). Further evidence on eye irritation is derived from the in vivo eye irritation data obtained from fossil diesel fuel (API, 1980b) similar to this substance.

In vitro eye irritation study was carried out using the SkinEthic reconstructed Human Corneal Epithelium Model (HCE, SkinEthic Laboratories, France) and in compliance with OECD principles of Good Laboratory Practice (GLP) (Warren, N., 2012). The principle of assay was based on the cytotoxicity in human cornel epithelial cultures following 10 minutes treatment of the test item by means of colourimetric MTT reduction assay. The relative mean viability of the test item treated tissues was 106.7 %. Based on this value the test item was considered to be non-irritant to the eye.

Since there is no in vivo data available from the substance, the eye irritation information from a read-across fossil diesel fuel, Fuel oil, no.2 i.e. #2 home heating oil (50% catalytically-cracked) is assessed (API, 1980b). A dose of 0.1 mL of undiluted test material was placed on the lower lid of the right eye of each of the nine rabbits. The left eye served as the control. In one male and two females, the test eye was flushed with distilled warm water 30 seconds after application. Only one rabbit, in the unrinsed group, exhibited minor conjunctival erythema at the 24 and 48 hour reading. All other animals were normal. Under the conditions of this study, the test material is not irritating to eyes.

Based on the in vivo data on the read-across substance and in vitro data on renewable hydrocarbons of wood origin (diesel type fraction) no classification is warranted for eye irritation.


Justification for selection of skin irritation / corrosion endpoint:
The selected study was conducted for read-across fossil diesel fuel (in vivo) showing skin irritation. This study was considered more reliable than the in vitro study conducted for the target substance that showed no evidence of skin irritation.

Justification for selection of eye irritation endpoint:
No study was selected since overall conclusion is based on the in vitro study conducted for the target substance and in vivo study conducted for the read-across substance.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the skin irritation information from read-across substances, renewable hydrocarbons of wood origin (diesel type fraction) has to be classified for Skin Irrit. 2 H315 according to CLP Regulation 1272/2008 and for Xi; 38 according to Directive 67/548/EEC.

Based on the eye irritation information from the substance itself and from read-across substances, renewable hydrocarbons of wood origin (diesel type fraction) has not to be classified for eye irritation according to CLP Regulation 1272/2008 and Directive 67/548/EEC.