Registration Dossier

Administrative data

Description of key information

Skin Irritation

Not irritating to the skin

 

Ocular Irritation

Not irritating to eyes

 

Respiratory Irritation

No studies were located to indicate that Hydrocarbons, C14 -C15, n-alkanes, <2% aromatics is a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 1984/05/23 and 1984/06/01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guideline N°404 but not in compliance with GLP.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Guideline study
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Ltd. Huntingdon; Cambridgeshire
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 2.1-2.3kg
- Housing: individually
- Diet (e.g. ad libitum): SDS, standard rabbit diet
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30-70 %
- Air changes (per hr): 19 times/hour
- Photoperiod (hrs dark / hrs light): 12 h/ 12h


IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
other: Electric clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL, undiluted
Duration of treatment / exposure:
4 hours
Observation period:
Skin reaction assessed at 1, 24, 48 and 72 hours, and 5, 10 days after exposure (after the removal of the patch)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm square gauze pads
- % coverage: no data
- Type of wrap if used: Each treatment site was occluded with "Elastoplast" elastic adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treatment site was washed using distilled water to remove any residual test substance
- Time after start of exposure: just after 4 hours exposure


SCORING SYSTEM: in accordance with the OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0.67 - <= 2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1.33
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
See Table I, the test substance is slightly irritating:
- Very slight reactions were seen in two animals during the 4 days observation period. The skin of both animals was normal on day 4
- Very slight erythema was seen in the third animal following removal of the bandage. By day 2, well defined erythema with slight oedema had developed and persisted to day 8. The skin was normal on day 10.
Other effects:
None

Table 5.2.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

24 h

1/1/2

0/0/0

48 h

1/1/2

0/1/2

72 h

0/0/2

0/1/2

Average 24h, 48h, 72h

0.67-0.67 -2

0-0.67 -1.33

Reversibility*

c

c

Average time (unit) for reversion

within day 10

within day 10

C: completely reversible

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, Petrepar-147 is not classified as skin irritant according to the criteria of Annex VI of the Directive 67/548/EEC and the CLP Regulation 1272/2008.
Executive summary:

In a primary dermal irritation study conducted according to OECD 404 without compliance in GLP, three rabbits were exposed to 0.5 mL of Petrepar-147. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 10 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 5 and 10 days after removal of the dressing. The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately.

The mean individual scores were 0.67, 0.67, 2.0 for erythema and 0.00, 0.67, 1.33 for edema. Skin reactions were totally reversible at day 10. Petrepar-147 is slightly irritating.

Based upon the directive 67/548/EEC and the CLP Regulation 1272/2008, Petrepar-147 is not considered as irritating to the rabbit skin.

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:
experimental study
Adequacy of study:
key study
Study period:
30 May to 6 June 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline N°405 but not in compliance with GLP. Substance analytical certificate provided by the manufacturer
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Guideline study
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Pemberley Rabbits, Cottenham, Cambridgeshire
- Age at study initiation: approximately 9 to 11 weeks
- Weight at study initiation: 2.1 to 2.5
- Housing: individually in metal cages with perforated floors
- Diet : Free access to SDS Standard Rabbit Diet
- Water : Free access to tap water
- Acclimation period: yes but no data on period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained at approximately 19°C
- Humidity (%): maintained at approximately 30-70%
- Air changes: maintained at approximately 19 air changes per hours
- Photoperiod (hrs dark / hrs light): lighting was controlled to give 12 hours of artificial light (07.00-19.00) in each 24 hour period

Vehicle:
not specified
Controls:
other: the contralateral eye remained untreated and served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
Duration of treatment / exposure:
7 days
Observation period (in vivo):
Examinations at 1, 24, 48, 72 hours and on Day 4 and 7.
Number of animals or in vitro replicates:
3 animals
Details on study design:
SCORING SYSTEM: as prescribed by OECD No 405 guideline

TOOL USED TO ASSESS SCORE: handheld torch
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
individual scores in all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: See Table 1 for details
Irritation parameter:
iris score
Basis:
mean
Remarks:
individual scores in all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: See Table 1 for details
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 mean individual score
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Remarks:
48 hours
Remarks on result:
other: See Table 1 for details
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: See Table 1 for details
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Remarks:
48 hours
Remarks on result:
other: See Table 1 for details
Irritation parameter:
chemosis score
Basis:
animal: #2, #3 mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: See Table 1 for details
Irritant / corrosive response data:
No corneal damage or iridal inflammation was observed. A diffuse crimson-red coloration of the conjunctivae was only observed in two animals one hour after instillation. Temporary mild conjunctival irritation was noted in the third animal. The eyes were normal 48 hours after instillation in all rabbits.
Other effects:
No other lesions

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

0/0/0

0/0/0

1/1/0

1/0/0

48 h

0/0/0

0/0/0

0/0/0

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0.0-0.0-0.0

0.0-0.0-0.0

0.33-0.33-0.0

0.33-0.0-0.0

Reversibility*)

-

-

48 h

48 h

Average time (unit) for reversion

-

-

c

c

*)Reversibility: c. = completely reversible; = not completely reversible; n. = not reversible

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Petrepar-147 is not classified as eye irritant according to the criteria of Annex VI of the Directive 67/548/EEC and the CLP Regulation 1272/2008.
Executive summary:

The eye irritant effect of Petrepar-147 was investigated according to the OECD Guideline No. 405 (1981).

Three albino rabbits were exposed to 0.1 mL of the test article in one eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 78 hrs and on day 4 and 7 after dosing. The eyes were not rinsed after administration of the test substance.

No corneal damage or iridal inflammation was observed. Redness and chemosis were observed in all animals, one hour after instillation. Slight redness was still observed in two animals at 24 hours while slight chemosis was only observed in one rabbit. The eyes of all rabbits were normal 48 hours after instillation. The mean individual scores were 0.33/0.33/0.0 for conjunctival redness and 0.33/0.0/0.0 for chemosis.

Petrepar-147 is not considered as irritating to the eyes according to Annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no skin/eye irritation data available for Hydrocarbons, C14-C15, n-alkanes, <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; C14-C16 n-Paraffins, Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics, and isohexadecane. This data is read across to Hydrocarbons, C14-C15, n-alkanes, <2% aromatics based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Skin irritation

Hydrocarbons, C14 -C17, n-alkanes, <2% aromatics

In a primary dermal irritation study conducted according to OECD 404 without compliance in GLP, three rabbits were exposed to 0.5 mL of Petrepar-147. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 10 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 5 and 10 days after removal of the dressing. The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately.

The mean individual scores were 0.67, 0.67, 2.0 for erythema and 0.00, 0.67, 1.33 for edema. Skin reactions were totally reversible at day 10. Petrepar-147 is slightly irritating.

Hydrocarbons, C14 -C16, n-Paraffins

In a primary dermal irritation study (EPA guidelines), six rabbits were exposed to 0.5 mL of C14 -C16 n-Paraffins , undiluted (intact site). Test sites were covered with a semi-occlusive dressing for 24 hours. Animals were observed for 14 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 5, 7 and 14 days after removal of the dressing. The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately.

Under these test conditions, the mean scores were 3 for erythema and 1.40 for oedema. At the final reading (14 days), yellow and red coloration (4 animals), slight fissuring (4 animals), leatheriness (6 animals) and desquamation (approx. 50% of area, 2 animals) at the skin treatment site were still observed. However, as the exposure to the test substance was 24 h and represents a major deviation, this study cannot be used for classification.

Hydrocarbons, C14 -C19, isoalkanes, cyclics, <2% aromatics

In a primary dermal irritation study conducted according to OECD guideline N°404, six young adult male New Zealand White rabbits were dermally exposed to 0.5 mL of MRD-94 -974. Test sites were covered with a semi-occlusive dressing for 4 hours. The skin reactions were assessed at 1, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times for all animals at 24, 48 and 72 hours after patch removal. The mean scores over 24, 48 and 72 hours were 0.0 for erythema and for oedema.

Isohexadecane

In a clinical test including 15 human volunteers, isohexadecane was applied undiluted on upper arm in occlusive consitions (patch) for 24 h. Skin reactions were scored 30 min and 24 h after removal of the patch. Mild signs of irritation were observed in only 3 volunteers and only slight signs of irritation in 8 volunteers in worse conditions (24-h exposure, occlusive conditions), leading to the conclusion that isohexadecane is not irritant for human skin.

The skin irritating properties of the substance BP solvent IH/isohexadecane was assessed in White Vienna rabbits (3 animals of both sexes). The test substance was applied on a wipe put in contact with the shaved skin under semi-occlusive dressing for 24 hours. At the end of exposure, skin reactions were recorded both at 24 hours (patch removal) and 48 hours after the end of exposure (i.e. 72 -hour time observation) according to the Draize scale. Complete observation time was 14 days. Moreover, the behavior, general state and food consumption were also observed. Body weight was measured every day. There was a very slight erythema (score 1) in two rabbits at patch removal (observation time = 24h). At the 72-hour observation, no erythema was observed in all 6 animals. No oedema was noted in any animal at any observation time.

No systemic effect was observed following exposure to BP Solvent IH/Isohexadecan. Behavior, general state, fur, food consumption and body weight development were normal.

Eye irritation

Hydrocarbons, C14 -C17, n-alkanes, <2% aromatics

The eye irritant effect of Petrepar-147 was investigated according to the OECD Guideline No. 405 (1981).

Three albino rabbits were exposed to 0.1 mL of the test article in one eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 78 hrs and on day 4 and 7 after dosing. The eyes were not rinsed after administration of the test substance.

No corneal damage or iridal inflammation was observed. Redness and chemosis were observed in all animals, one hour after instillation. Slight redness was still observed in two animals at 24 hours while slight chemosis was only observed in one rabbit. The eyes of all rabbits were normal 48 hours after instillation. The mean individual scores were 0.33/0.33/0.0 for conjunctival redness and 0.33/0.0/0.0 for chemosis.

Hydrocarbons, C14 -C16, n-Paraffins

C14-C16 n-Paraffins were instilled undiluted (0.1 mL) into the conjunctival sac of New Zealand White rabbits.

Following the test substance instillation, the treated eyes remained unwashed in the first group of six animals. In this case, the test substance produced minimal erythema of the conjunctivae (score 1) in all animals and barely perceptible to minimal chemosis only in two animals within 24 hours. The ocular lesions were totally reversed in the six animals within the post-instillation 72-hour observation period (after 48 hours in five animals and after 72 hours in the last animal). The mean scores were 0.38 for conjunctival redness and 0.11 for chemosis.

In the second group of three rabbits, the treated eyes were washed with tap water 20 seconds after instillation of C14-C16 n-Paraffins (0.1 mL). Chemosis, corneal and iridal lesions were not observed in all rabbits through out the observation period. Slight conjunctival redness was only observed at 24 hours in all animals. The treated eyes returned to a sign-free condition in all animals at forty­eight hours: the mean individual scores were 0.33-0.33-0.33 over the 24 to 72 hours.

Isohexadecane

The irritant potential of the substance BP Solvent IH/Isohexadecane was assessed by applying 0.1 mL of the test substance in the conjunctival sac of the left eye of 6 male Himalayan rabbits. After application the animals lid were kept closed for 1 second. The right eye was used as control and received 0.1 mL of physiological NaCl solution.

The eyes were examined and the changes were graded according to a numerical scale at 15 min, 1, 24, 48 and 72 hours after dosing.

No conjunctival chemosis, corneal and iridal lesion were observed throughout the observation period. Slight redness of the conjunctivae was observed in all animals at 1 hour but only in one animal by the 24 hours after instillation. At 48-hour observation period, no redness was observed in any rabbit. Hence, the mean individual score for redness was 0.33-0.0-0.0.

Respiratory Irritation:

no studies available

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, Hydrocarbons, C14-C15, n-alkanes, <2% aromatics do not meet the criteria for classification for skin Irritation under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Eye Irritation:

Based on available read across data, Hydrocarbons, C14-C15, n-alkanes, <2% aromatics do not meet the criteria for classification as ocular irritants under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Respiratory Irritation:

There are no studies that warrant classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).