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Administrative data

Description of key information

Skin Irritation – not a dermal irritant


Ocular Irritation - not an ocular irritant


Respiratory Irritation - not a repiratory 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:
experimental study
Adequacy of study:
key study
Study period:
Oct. 2, 1990- Oct. 23, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ray Nichols Rabbitry, Lumberton, TX
- Age at study initiation: 3-6 months
- Weight at study initiation: N/A
- Housing: Singly in wire-bottomed, suspended, stainless steel cages, identified by ear tags
- Diet (e.g. ad libitum): Purina Rabbit Chow in measured amounts
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: one week

IN-LIFE DATES: From: Oct. 2, 1990 To: Oct. 23, 1990
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: control area on each test animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml undiluted
Duration of treatment / exposure:
4 hrs
Observation period:
21 days
Number of animals:
6 - 3 males, 3 females
Details on study design:
TEST SITE
- Area of exposure: An 8 x 8 cm dorsal area of the trunk was clipped. Part of this area was used as a control.
- % coverage: An approximately 2.5 x 2.5 cm area of the trunk was covered.
- Type of wrap if used: Test material was placed beneath two single layers of surgical gauze which were secured with non-irritating adhesive tape. Trunks of the animals were wrapped with semi-permeable dressing held in place with non-irritating adhesive tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were washed with room temperature tap water and wiped with a wet cloth.
- Time after start of exposure: 4 hrs


SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1.22
Max. score:
2
Reversibility:
other: 21 days
Remarks on result:
other: Fully reversible in all but 2 animals (very minor redness observed)
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
All animals showed very slight erythema/eschar at the 3-4 hrs observation. This persisted in all animals until at least day 10, with some animals showing an increase to a score of 2. The erythema/eschar did not resolve in two of the animals by the end of the experiment at day 21. Two animals showed very slight edema at the .75 hr observation, with all animals showing this at the 24 hr observation. The edema symptoms did not worsen, and resolved in all animals by day 21.
Other effects:
No other effects were seen in any animal at any observation.

Animal

Observation

Hours

Days

3-4

24

48

72

7

10

14

17

21

9918-M

Erythema/eschar

1

1

1

1

1

0

0

0

0

Edema

0

1

1

1

1

1

0

0

0

9920-M

Erythema/eschar

1

1

1

1

1

1

1

1

0

Edema

0

1

1

1

1

1

0

0

0

9922-M

Erythema/eschar

1

1

1

1

1

1

1

1

1

Edema

1

1

1

1

1

1

0

0

0

9913-F

Erythema/eschar

1

2

2

2

1

1

1

1

0

Edema

0

1

1

1

1

1

0

0

0

9915-F

Erythema/eschar

1

1

1

1

2

2

1

1

0

Edema

0

1

1

1

1

1

0

0

0

9917-F

Erythema/eschar

1

1

1

2

2

2

1

1

1

Edema

1

1

1

1

1

1

1

1

0

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
The average erythema score was calculated using the scores from the 24, 48, and 72 hr observations was 1.22 and the average edema score was calculated as 1.0. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

This study examined the skin irritancy of MR Solvent to rabbit skin. 3 male and 3 female rabbits were exposed dermally to 0.5 ml of test substance for 4 hrs. Test substance was applied to a clipped dorsal area and the area occluded. After 4 hrs, the test areas were washed with tap water. Once the test substance was removed, the animals were scored for skin irritation. Additional observations were made at 24, 48, and 72 hrs, and 7, 10, 14, 17, and 21 days after removal. Animals exhibited very slight erythema and edema (score of 1) beginning at the first observation. By the 24 hr observation, some of the erythema scores had risen to 2, which reversed by day 10. All edema symptoms had resolved by day 21, however, two animals still had very slight redness on day 21. No other signs of skin irritation were seen. The average erythema score was calculated using the scores from the 24, 48, and 72 hr observations was 1.22 and the average edema score was calculated as 1.0. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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:
experimental study
Adequacy of study:
key study
Study period:
Oct. 1, 1990 - Oct. 4, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ray Nichols Rabbitry, Lumberton, TX
- Age at study initiation: 3-6 months
- Weight at study initiation: N/A
- Housing: Singly in wire-bottomed, suspended, stainless steel cages, identified by ear tags
- Diet (e.g. ad libitum): Purina Rabbit Chow in measured amounts
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: one week

IN-LIFE DATES: From: Oct. 1, 1990 To: Oct. 4, 1990
Vehicle:
unchanged (no vehicle)
Controls:
other: the non-treated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
The eyes of 3 of the nine animals were washed for one minute with room temperature deionized water 30 seconds after start of exposure. The eyes of the remaining 6 animals were unwashed.
Observation period (in vivo):
72 hrs at which time no animals showed signs of irritation.
Number of animals or in vitro replicates:
9 animals total
3 males and 3 females were used in the unwashed eye experiment
3 males were used in the washed eye experiment
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of 3 of the nine animals were washed for one minute with room temperature deionized water. The eyes of the remaining 6 animals were unwashed.
- Time after start of exposure: 30 seconds after start of exposure


SCORING SYSTEM: According to EPA guidelines 81-4


TOOL USED TO ASSESS SCORE: All animals were examined with 0.2% fluorescein sodium ophthalmic solution at the 24 hr observation . Since no fluorescein staining was seen in any animal, the examination was not repeated at later observations.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hrs
Remarks on result:
other: unwashed eyes
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: unwashed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: unwashed eyes
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0
Max. score:
0
Remarks on result:
other: unwashed eyes
Irritant / corrosive response data:
All six of the unwashed animals showed redness (score of 1) at the 1 and 24 hr observations. The three females and one male also showed chemosis (score of 1) at the 1 hr observation. All symptoms were resolved at the 48 hr observation. All three washed animals showed redness (score of 1) at the 1 and 24 hr observation. These symptoms were also resolved by the 48 hr observation.
Other effects:
No other effects were observed in any animal at any observation.

Individual Eye Irritation Scores - Washed

Animal

1 hr

24 hrs

48 hrs

72 hrs

9960-M

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

0

0

0

0

Conjunctiva, discharge

0

0

0

0

9962-M

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

0

0

0

0

Conjunctiva, discharge

0

0

0

0

9964-M

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

0

0

0

0

Conjunctiva, discharge

0

0

0

0

Individual Eye Irritation Scores - Unwashed

Animal

1 hr

24 hrs

48 hrs

72 hrs

9954-M

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

1

0

0

0

Conjunctiva, discharge

0

0

0

0

9956-M

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

0

0

0

0

Conjunctiva, discharge

0

0

0

0

9958-M

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

0

0

0

0

Conjunctiva, discharge

0

0

0

0

9957-F

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

1

0

0

0

Conjunctiva, discharge

0

0

0

0

9959-F

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

1

0

0

0

Conjunctiva, discharge

0

0

0

0

9961-F

Cornea, opacity

0

0

0

0

Cornea, area

0

0

0

0

Iris

0

0

0

0

Conjunctiva, redness

1

1

0

0

Conjunctiva, chemosis

1

0

0

0

Conjunctiva, discharge

0

0

0

0

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
Mean scores for redness at 24, 48, 72 hours were 0.33, 0.33, and 0.33 respectively. The mean erythema score was 0.33. The scores for chemosis were 0, 0, and 0. The mean erythema score was 0.0. There were no positive scores for corneal, or iridial irritation. Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Application of 0.1ml of MRD-89-523 to the eye of six rabbits elicited slight, transient conjunctival redness, chemosis, and some discharge. Mean scores for redness at 24, 48, 72 hours were 0.33, 0.33, and 0.33 respectively.  The mean erythema score was 0.33. The scores for chemosis were 0, 0, and 0.  The mean erythema score was 0.0. There were no positive scores for corneal, or iridial irritation.  Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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 adverse effect observed (not irritating)

Additional information

Skin Irritation – C9-C14 Aliphatics (2-25% Aromatics) are not corrosives or dermal irritants for rabbit (OECD TG 404). The average (24, 48, 72 hours) erythema score was found to be 1.22 and the average edema score was 0.3. 

 

Ocular Irritation - C9-C14 Aliphatics (2-25% Aromatics) are not irritating for rabbits (OECD TG 405). The average (24, 48, 72 hours) conjuctivae score was found to be 0.3, the average chemosis score was 0, and there was no indication of iris or cornea irritation (scores of 0). 

 

Respiratory Irritation

Human Exposure - There are no reports of respiratory irritation in humans associated with exposure to C9-C14 aliphatic solvents. Two studies have been reported in which volunteers were exposed to C9-C14 aliphatic solvents at differing concentrations. In the first of these, 6 volunteers were exposed for 15 minutes at levels ranging from 24-470 ppm (126-2468 mg/m3) and, after exposure, asked to report their symptoms. There were no reports of throat irritation at the two lower concentrations and only one of the 6 reported throat irritation at the highest level (Carpenter et al., 1975). In the second study (Lammers et al., 2007), there was no evidence of respiratory irritation in volunteers at levels of 570 mg/m3. 

 

Animal Exposure - In the first of these studies (Carpenter et al., 1975a), a 50% depression in respiratory rate was observed in mice exposed to 10,000 mg/m3 (1700 ppm), but not at 4.4 mg/l (770 ppm). In the second of these studies (ExxonMobil Biomedical Sciences, Inc., 1988), a maximum exposure concentration of 170 ppm (935 mg/m3) produced a respiratory depression of 15%, a response which was considered to be slightly irritating. 

 

Taken as a whole, the animal data suggest that C9-C14 aliphatic solvents are not highly irritating to the respiratory tract and certainly not at occupational levels. The results of the volunteer studies demonstrate that C9-C14 aliphatic solvents are not respiratory irritants to humans.

Justification for classification or non-classification

These findings do not warrant the classification of C9-C14 Aliphatics (2-25% Aromatics) as skin, ocular, or respiratory irritants under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

 

SKIN IRRITATION: Erythema and edema scores (24, 48, and 72 average) are below the classification threshold requirements: 2.0, Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparation; 2.3, the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP)

 

OCULAR IRRITATION: Ocular lesion scores (24, 48, and 72 average) are below the classification threshold requirements.

Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparation: 0, cornea opacity; 0, iris lesion; >2.5, redness of the conjunctivae; >2.0, oedema of the conjunctivae (chemosis).

Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP): 0, cornea opacity; 0, iris lesion; >2.0, redness of the conjunctivae; >2.0, oedema of the conjunctivae (chemosis).

 

RESPIRATORY IRRITATION - There are no studies that warrent classification as a respiratory irritant under either the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC or under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).