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

Endpoint summary

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-C19, isoalkanes, cyclics, <2% aromatics is a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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 1998/09/14 to 1998/09/25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD guideline N°404 in compliance with GLP. Substance analytical certificate not available

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Guideline study

GLP compliance:

yes

Species:

rabbit

Strain:

other: SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Russian from Mollegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved.
- Age at study initiation: no data
- Weight at study initiation: 2.1-2.5 kg
- Housing: individually
- Diet (e.g. ad libitum): A pelleted complete rabbit "Altromin 2123" diet ad libitum
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 10 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 7 days after exposure (after the removal of the patch)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: ca. 2.5 cm X 2.5 cm (left+ right)
- % coverage: no data
- Type of wrap if used: Nobifix (6 cm width) was loosely wound round the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test substance was cleaned with lukewarm water and mild soap
- Time after start of exposure: 4 hours


SCORING SYSTEM: in accordance with the OECD guideline 404

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

See Table I, the test substance is slightly irritating:
- The mean individual erythema scores were 0.2, 0.3 and 0.5 respectively
- The mean individual oedema scores were 0.7, 0.0 and 0.0 respectively

Other effects:

none

Table I: 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	L: 1/1/1      R: 0/1/1	L and R: 0/0/0
48 h	L: 0/0/0      R: 0/0/1	L: 1/0/0 R: 1/0/0
72 h	L: 0/0/0       R: 0/0/0	L: 1/0/0 R: 1/0/0
Average 24h, 48h, 72h	L+R: 0.2 -0.3- 0.5	L and R: 0.7-0-0
Reversibility*	C	C
Average time (unit) for reversion	within 72 hours	within 7 days

L: left test flank R: right test flank C: completely reversible

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, DEV 98-25 is not classified as skin irritant according to the criteria of Annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.

Executive summary:

In a primary dermal irritation study conducted according to OECD guideline N°404, three rabbits were exposed to 0.5 mL of DEV 98-25 at two skin sites on the back.

Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 7 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 7 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 0.2, 0.3 and 0.5 for erythema and 0.7, 0.0 and 0.0 for edema.

Based upon the directive 67/548/EEC and the CLP Regulation 1272/2008, DEV 98 -25 is not considered as irritating to the rabbit skin.

Reference 2

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

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

28 September 1998 to 02 October 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline N°405, GLP but substance analytical certificate not available (Substance identification: code name with information on test substance).

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:

yes

Remarks:

age of animals at study initiation was not reported

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

age of animals at study initiation was not reported

Principles of method if other than guideline:

Guideline study

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: SPF albino rabbits of the stock Mol:Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: M & B, Ejby, DK-4623 Lille Skensved, Denmark
- Age at study initiation: no data
- Weight at study initiation: 2.3 - 2.8 kg
- Housing: kept individually in PPO/HIPS cages (Noryl, floor area = 2576 cm²)
- Diet: pelleted complete rabbit diet "Altromin 2123" from Ch. Petersen ad libitum. Analysis for major nutritive components and relevant possible contaminations in the diet are performed regularly.
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5 ad libitum. Analyses for relevant possible contamination in the water are performed regularly.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): 10
- Photoperiod :12 hrs dark /12 hrs light


IN-LIFE DATES: From: To:

Vehicle:

not specified

Controls:

other: the right eye of the treated animals was used as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48, 72 hours after application

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with 20 mL 0.9% sodium chloride solution
- Time after start of exposure: 24 hrs


SCORING SYSTEM: grading according to OECD 405 recommendation


TOOL USED TO ASSESS SCORE: fluorescein, UV light

Irritation parameter:

cornea opacity score

Basis:

other: mean individual score for all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: See Table 1 for details

Irritation parameter:

iris score

Basis:

other: mean individual score for all animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: See Table 1 for details

Irritation parameter:

chemosis score

Basis:

other: mean individual score for all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: See Table 1 for details

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #3 - Mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

other: See Table 1 for details

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

other: See Table 1 for details

Irritant / corrosive response data:

Irritant effects on conjunctiva (redness) were minimal at 1 hour in all animals and were fully reversed at 72h in all animals. There were no effects on the cornea and the iris at any time point. Chemosis was not observed at any time point in all animals.
It can be concluded that DV 98-25 would not be classified as eye irritant.

Other effects:

No data

Table 1: DV 98 -25 Acute eye irritation/corrosion study in the rabbit. Scores for ocular lesions.

Rabbit No /			1 h	24 hrs		48 hrs	72 hrs	Individual mean score*
weight (kg)					F
3531 / 2.3	Cornea opacity, area		0	0	0	0	0
	Cornea opacity, degree		0	0	0	0	0	0.0
	Iris		0	0		0	0	0.0
	Conjunctiva	Chemosis	0	0		0	0	0.0
		Redness	1	0		0	0	0.0
		Discharge	3	0		0	0
3533 / 2.3	Cornea opacity, area		0	0	0	0	0
	Cornea opacity, degree		0	0	0	0	0	0.0
	Iris		0	0		0	0	0.0
	Conjunctiva	Chemosis	0	0		0	0	0.0
		Redness	1	1		1	0	0.7
		Discharge	3	0		0	0
3534 / 2.8	Cornea opacity, area		0	0	0	0	0
	Cornea opacity, degree		0	0	0	0	0	0.0
	Iris		0	0		0	0	0.0
	Conjunctiva	Chemosis	0	0		0	0	0.0
		Redness	1	0		0	0	0.0
		Discharge	3	0		0	0	0.0

F: Reading after instillation of oculoguttae fluoresceini.

* Only the scores from the 3 readings (24, 48 and 72 hours) are included in the calculation of the individual mean scores

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

under the test conditions, DV 98-25 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 DV 98-25 was investigated according to the OECD Guideline No. 405 (1987) and EEC B.5 method (1992) and in compliance with Good Laboratory Practice.

Three female albino rabbits were exposed to 0.1 mL of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours after dosing.

Minimal conjunctival irritation (redness) was observed in the three rabbits 1 hour after dosing. During the rest of the observation period no abnormalities were observed for two animals while redness (score 1) was still observed up to 48 h in the third animal.

DV 98 -25 is not considered as irritating to the eyes according to Annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.

Reference 2

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

Supporting skin and no eye irritation data is available for Hydrocarbons C14-C19, isoalkanes, cyclics, <2% aromatics. However, key and supporting data is available for structural analogues, Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, < 2% aromatics; C14-C16, n-paraffins; and Isohexadecane and presented in the dossier. This data is read across to Hydrocarbons C14-C19, isoalkanes, cyclics, <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-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a key primary dermal irritation study conducted according to OECD guideline N°404, three rabbits were exposed to 0.5 mL of the test material (Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics) at two skin sites on the back (TOTAL Solvants, 1998). Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 7 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 7 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 0.2, 0.3 and 0.5 for erythema and 0.7, 0.0 and 0.0 for edema. Based upon the criteria of CLP Regulation 1272/2008, Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics is not considered as irritating to the rabbit skin.

 

Additionally, eight supporting and reliable studies are available for skin irritation, dealing with the toxicity of Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics. All studies were conducted similarly or according to OECD guideline 404. All studies show no or slight irritation effects on rabbits' skin.

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.

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-C19, isoalkanes, cyclics, <2% aromatics

In a supporting primary dermal irritation study (ExxonMobil, 1995) conducted according to OECD guideline N°404, six young adult male New Zealand White rabbits were dermally exposed to 0.5 mL of the test material (Hydrocarbons C14-C19, isoalkanes, cyclics, <2% aromatics ). 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. Based upon the criteria of the CLP Regulation 1272/2008, Hydrocarbons, C14 -C19, isoalkanes,

cyclics, <2% aromaticsis not considered as irritating to the rabbit skin.

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-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a key study (TOTAL Solvants, 1998), the eye irritant effect of the test material (Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics) was investigated according to the OECD Guideline No. 405 (1987) and EEC B.5 method (1992) and in compliance with Good Laboratory Practice. Three female albino rabbits were exposed to 0.1 mL of the test material in the left eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours after dosing. Minimal conjunctival irritation (redness) was observed in the three rabbits 1 hour after dosing. During the rest of the observation period no abnormalities were observed for two animals while redness (score 1) was still observed up to 48 h in the third animal. Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics is not considered as irritating to the eyes according to the criteria of CLP Regulation 1272/2008.

 

Additionally, four supporting studies are available for eye irritation, dealing with the toxicity of Hydrocarbons C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics. All studies were conducted similarly or according to OECD guideline 405. All studies show no or slight irritation effects on rabbits' eyes.

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.

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).

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 Hydrocarbons C14-C19, isoalkanes, cyclics, <2% aromatics is a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on the available substance specific and read across data, Hydrocarbons C14-C19, isoalkanes, cyclics, <2% aromatics 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, Hydrocarbons C14-C19, isoalkanes, cyclics, <2% aromatics 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).