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Administrative data

Description of key information

In two in vivo skin irritation studies in rabbits, MPD was considered non-irritant. 
In an in vivo eye irritation study in rabbits (GLP and OECD TG 405) MPD was considered non-irritating. A supporting in vivo eye study in rabbits (no GLP and similar to OECD TG 405) reported MPD as being irritating and effects not beeing reversible after 7 days.

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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test method.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): 3-Methyl-1,5 pentanediol
- Physical state: clear, colorless liquid
- test substance recieved on (date): 1 July 1987
- Sample designation: 3-Methyl-1,5-pentanediol
- Purity: > 99%
- Stability under test conditions: the stability and absorption of the test substance were not determined
- Storage condition of test material: at ambient temperature
- Other: the test substance was administered as supplied by the sponsor
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: three New Zealand White rabbits (from Buckmaster, Henham, Hertfordshire, England)
- Age at study initiation: approx. 9 to 10 weeks
- Weight at study initiation: approx. 2.0 to 2.3 kg prior to treatment
- Housing: individually housed in metal cages
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet
- Water (e.g. ad libitum): tap water
- Acclimation period: acclimated to the laboratory environment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 19 per hr
- Photoperiod (hrs dark / hrs light): 12 hr light/ 12 hr dark
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml aliquot of 3-methyl-1,5-pentanediol
Duration of treatment / exposure:
4 hr
Observation period:
Examination of the treated skin was made on day 1 (approx. 30 minutes after removal of the patches), 2, 3 and 4.
Number of animals:
3
Details on study design:
Rabbits were dosed with 0.5 ml of the test substance. The dose was applied under a 2.5 cm square gauze pad to a clipped, intact skin site of each animal. Each treatment site was occulded with "Elastoplast" elastic adhesive dressing for a four hour period. At the end of the exposure period, the semi-occulsive dressing and gauze pad were removed and the treatment site was washed using water to remove any residual test substance.

Examination of the treated skin was made on day 1 (approx. 30 minutes after removal of the patches) and on days 2, 3, and 4


Grading and scoring of the dermal reactions were performed using the prescribed numerical scoring system as follows:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries 4
in depth)

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending 4
beyond the area of exposure)

Interpretation of results and classification of substance
The results obtained were evaluated taking into consideration the nature and the reversibility or irreversibility of the findings observed. Classification of the substance is based on the criteria laid down in: Regulation 1272/2008 EC, Annex I, table 3.2.2

Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 hr
Remarks on result:
other:
Remarks:
first reading taken approx 30 mins after removal of dressing
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 hr
Remarks on result:
other:
Remarks:
first reading taken approx 30 mins after removal of dressing
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24hr
Remarks on result:
other:
Remarks:
first reading taken approx 30 mins after removal of dressing
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: see Remarks
Remarks on result:
no indication of irritation

Very slight erythema was observed in all three animals on Day 1. The reactions had resolved by Day 2.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions described in this study report, 3-methyl-1,5-pentanediol was considered as non-irritant when applied to the skin of rabbits.
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:
supporting study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited documentation, 0.05 mL application amount, 8 day observation period)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(limited documentation, 0.05 mL application amount, 8 day observation period)
GLP compliance:
no
Specific details on test material used for the study:
- Name of test substance (as cited in study report): 3-Methylpentanodiol-1,5
- Analytical purity: 99.5%
- Physical state: liquid
- Density: 0.973 g/mL
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: 3.27 and 2.77 kg (first experiment); 3.45 kg and 3.43 kg (second experiment)
no additional details reported
Vehicle:
unchanged (no vehicle)
Controls:
other: other eye of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
one single application
Observation period (in vivo):
8 days
- Readings, first experiment: 10 min; 1, 3, 24 and 72 h, day 6 and 8
- Readings, second experiment: 10 min; 1, 3, 24, 48 and 72 h; day 4, 7 and 8
Number of animals or in vitro replicates:
4 males (2 in each experiment)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: evaluation was performed according to the Draize Scoring System

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(out of animal#3 and #4)
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days

Table 1: Eye irritation: Details on result                                                                                                                   

Exp. 1

Reading

Animal#1

Animal#2

Cornea

Chemosis

Iris

Conjunctivae

Cornea

Chemosis

Iris

Conjunctivae

10 min

0

1 SD

0

1

0

1 SD

0

1

1 h

0

2 SD

0

1

0

2 SD

0

1

3 h

0

2 SD

0

1

1

1 SD

0

1

24 h

1

2 SD

0

2

1

1 SD

0

2

72 h

1

0 SD

0

1

1

0 SD

0

1

Day 6

0

0

0

1

1 SC

0

0

1

Day 8

0

0

0

0

1 SC

0

0

1

Mean (24 – 72 h)

1.0

1.0

0.0

1.5

1.0

0.5

0.0

1.5

Mean (animal #1 and 2)

1.0

0.75

0.0

1.5

 

Exp. 2

Reading

Animal#3

Animal#4

Cornea

Chemosis

Iris

Conjunctivae

Cornea

Chemosis

Iris

Conjunctivae

10 min

0

1 SD

0

1

0

1 SD

0

1

1 h

0

2 S

0

1

0

1 S

0

1

3 h

1

2 SD

0

1

1

1 SD

0

1

24 h

1

2 S

1

2

1

1 S

1

1

48 h

2

1 SD

0

2

2

1 SD

0

2

72 h

2

1 SD

0

2

2

1 SD

2

2

Day 4

2 SC

0

0

2

2

1 SD

2

2

Day 7

1 SC

0

0

1

2 SC

0

0

1

Day 8

1 SC

0

0

1

1 SC

0

0

1

Mean (24 – 72 h)

1.67

1.33

0.33

2.00

1.67

1.00

1.00

1.67

Mean (animal #3 and 4)

1.67

1.17

0.67

1.84

 

SD = smeary deposit; S = secretion; scar formation

Evaluation was performed based on the results with animal#3 and animal#4 (experiment 2), because scoring was performed at all relevant time points and the reactions were stronger than with animal#1 and 2. Scar formation was not considered, because sight was not affected.

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Therefore, classification for eye irritation is warranted as follows:
CLP: Category 2
GHS (UN): Category 2A
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are no reports of human eye, skin or respiratory irritation associated with MPD exposure. MPD has been tested on animals and the results demonstrate that this substance is not a acute skin irritant (Huntingdon (1987), 871011D).

Skin irritation

Semiocclusive application of MPD (Michael P. Liggett; Paul A. Smith (1987)) on 3 New Zealand White Rabbits for 4 hours (according to OECD TG 404) resulted in erythema score of 1/4 on day 1 (approximately 30 min after removal of the dressing) and 0/4 on day 2, 3, and 4. day 1. The very slight erythema observed in all three animals on Day 1 resolved by day 2. An edema score of 0/4 were observed on day 1, 2, 3 and 4. In a supporting study (BASF AG (1976)) according to OECD TG 404 similar results were observed.

Eye irritation

MPD was tested (Michael P. Liggett; Paul A. Smith (1987)) in the key in vivo test in rabbits (according to OECD TG 405 and GLP). The mean score for cornea opacity was above 1.0 for one rabbit and the mean score for iris and conjunctivae redness/chemosis was lower than 1 or 2, respectively on day 1, 2 and 3. Corneal opacity and conjunctivae redness and chemosis were fully reversible within 7 days.

In a supporting in vivo test (Dr. med Hofmann; Dr. rer. nat. Munk (1976)) with rabbits (similar to OECD TG 405 and non GLP), the mean score for cornea opacity was above 1.0 and not fully reversible within the observation period of 8 days and the score for iris for one animal was 1 and fully reversible within 7 days. The score for one animal for conjunctivae redness was 2 and not fully reversible whithin the observation period of 8 days. The result of the supporting study demonstrates that the substance is eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Two studies are available. Both studies concur with rating the substance as non-irritant. The more reliable study was selected.

Justification for selection of eye irritation endpoint:
Although a reliable study reports eye irritation which is fully reversible after seven days, a second available study eye irritation was not reversible after 7 days. The more sensitive endpoint was chosen.

Effects on eye irritation: irritating

Justification for classification or non-classification

Two valid studies are available for eye irritation with rabbits following OECD 405. One shows fully reversible effects of corneal opacity, iritis and conjunctival redness/chemosis within 7 days, the second study considers MPD to be irritating to the eyes. As long as no human data or further studies are available a worst case approach is adopted and the classification as Eye irritant (Cat. 2) is concuded following 1272/2008/EC and 67/578/EEC.