Registration Dossier

Diss Factsheets

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 Isohexadecane is a respiratory irritant.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 30th of April to 3rd of May 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Method similar as OECD guideline N°404 in compliance with GLP. Six rabbits were treated. Substance identification: code name with commercial substance name. Substance analytical certificate not available in the report
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
One rabbit was sacrificed by cardiac puncture. The authors considered this deviation is not pertinent.
Principles of method if other than guideline:
Guideline principles
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Denver, PA
- Age at study initiation: approximately 12 weeks
- Weight at study initiation: 1.85 to 2.29 kg
- Housing: individual
- Diet (e.g. ad libitum): Agway Certified Diet R.C.A. Rabbit, restricted feeding regimen
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): from 65 to 70°F
- Humidity (%): maintained range of 40 to 60% relative humidity
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): approximately 12 hours light and 12 hours dark

Type of coverage:
semiocclusive
Preparation of test site:
other: electric clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL dose
- Concentration (if solution): substance tested undiluted (as supplied)
Duration of treatment / exposure:
Approximately 4 hours of exposure.
Observation period:
Dermal responses were evaluated approximately 45 minutes, 24, 48 and 72 hours following patch removal.
Number of animals:
6 females.
Details on study design:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: no data


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed, using reverse osmosis water and papers towels.
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to the Draize Method of Scoring.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No animal death prior to study termination.
Topical application of MRD-90-903 elicited no responses in any animal.
Other effects:
No additional data.

Table 7.3.1/1: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

0/0/0/0/0/0

0/0/0/0/0/0

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

Reversibility*

-

-

Average time (unit) for reversion

-

-

*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:
Under the test conditions, MRD-90-903 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 as similar to OECD guideline N°404 in compliance with GLP, six young adult female New Zealand White rabbits were dermally exposed to 0.5 mL of MRD-90-903. Test sites were covered with a semi-occlusive dressing for 4 hours. The skin reactions were assessed at 45 minutes, 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.

Based upon the directive 67 /548/EEC and the CLP Regulation 1272/2008, MRD-90-903 is not considered as irritating to the rabbit skin.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from 1995/11/15 to 1995/11/18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study similar to OECD guideline n°404 without any deviation
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Guideline principles
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products
- Age at study initiation: approximately 15 weeks
- Weight at study initiation: 2.58-3.05kg
- Housing: individually
- Diet (e.g. ad libitum): Agway certified diet R.C.A.Rabbit (pellets), restricted as per recommendation of supplier
- Water (e.g. ad libitum): Automatic watering system, ad libitum
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65 to 70 °F
- Humidity (%): 40 - 60 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h/ 12h


IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
shaved
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:
45 min, 20, 44 and 72 hours post application and once on day 7
Number of animals:
3 males + 3 females
Details on study design:
TEST SITE
- Area of exposure: a single dose introduced under a gauze patch and held in contact with the skin.
- % coverage: no data
- Type of wrap if used: no irritating tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was then removed
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize scale for dermal irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Topical application of MRD-90-903 elicited very slight erythema at the 45 min observation point in 3 animals. All symptoms reversed by the 24 hour observation point. No edema was noted for any of the animals.
Other effects:
none

No data

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the test condition, MRD-90-903 is not irritating according to the directive 67/548/EEC and to the CLP Regulation 1272/2008.
Executive summary:

In a primary dermal irritation study according to OECD guideline 404, young adult New Zealand White rabbits (3 males + 3 females) were dermally exposed to 0.5 mL of MRD-90-903. Test sites were covered with a semi-occlusive dressing for 4 hours. Dermal responses were evaluated at 45 min, 24, 48, and 72 hours post-dosing according to the Draize method of scoring.

Very slight erythema was observed at 45 min in 3 animals, all symptoms reversed by 24 hours. Edema was not noted in any of the animals. The individual mean score for erythema/eschar and oedema for each of the 3 animals was 0

Based upon the directive 67/548/EEC and the CLP Regulation 1272/2008, MRD-90-903 is not considered as irritating to the rabbit skin.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
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:
read-across from supporting substance (structural analogue or surrogate)
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:
The justification for read across is provided 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:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Only supporting skin and eye irritation data is available for Isohexadecane. Data is also available for structural analogues, Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, < 2% aromatics; and C14-C16, n-paraffins and presented in the dossier. This data is read across to Isohexadecane 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 (Petroquimica, 1984). 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 (Conoco., Inc., 1982). 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.

Isohexadecane

In a clinical test including 15 human volunteers, isohexadecane was applied undiluted on upper arm in occlusive consitions (patch) for 24 h (Hill Top Research, 1994). 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. No systemic effect was observed following exposure to BP Solvent IH/Isohexadecan. Behavior, general state, fur, food consumption and body weight development were normal (INEOS, 1980).

Hydrocarbons, C16 -C20, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a primary dermal irritation study conducted as similar to OECD guideline N°404 in compliance with GLP, six young adult female New Zealand White rabbits were dermally exposed to 0.5 mL of MRD-90-903 (ExxonMobil, 1991a). Test sites were covered with a semi-occlusive dressing for 4 hours. The skin reactions were assessed at 45 minutes, 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.

 

In a primary dermal irritation study according to OECD guideline 404, young adult New Zealand White rabbits (3 males + 3 females) were dermally exposed to 0.5 mL of MRD-90-903 (ExxonMobil, 1991b). Test sites were covered with a semi-occlusive dressing for 4 hours. Dermal responses were evaluated at 45 min, 24, 48, and 72 hours post-dosing according to the Draize method of scoring.Very slight erythema was observed at 45 min in 3 animals, all symptoms reversed by 24 hours. Edema was not noted in any of the animals. The individual mean score for erythema/eschar and oedema for each of the 3 animals was 0.

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 (Petroquimica, 1984).

Hydrocarbons, C14 -C16, n-Paraffins

 

C14-C16 n-Paraffins were instilled undiluted (0.1 mL) into the conjunctival sac of New Zealand White rabbits (Conoco., Inc., 1982). 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 (INEOS, 1980). 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 were located to indicate that Isohexadecane is a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on the available substance specific and read across data, Isohexadecane does 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 the available substance specific and read across data, Isohexadecane does not meet the criteria for classification as an ocular irritant 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).