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Description of key information

Pentaerythritol was shown to be non-irritating to rabbit skin and the rabbit eye.  There is no evidence from worker exposure that the substance causes respiratory irritation.

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:
09 September 1982 to 23 September 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP but guideline-comparable proprietray study
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECO Guideline for Testing of Chemicals. OECO, ISBN-92-64-12221-4 (1981)
Qualifier:
equivalent or similar to guideline
Guideline:
other: Draize, J.H. In appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, 46-59, Association of Food and Drug Officials of the United States, Topeka, Kansas 1995
Qualifier:
equivalent or similar to guideline
Guideline:
other: Draize, J.H., Woodward, G. and H.O. Calvery, J. Pharmacol. Exp. Therap., 82, 377-390 (1944)
Principles of method if other than guideline:
The test was carried out on the instructions of the Specialist Department of Industrial
Toxicology of Degussa, Frankfurt/Main. It was carried out after a single application of the test product to the intact and scarified skin on the back of a rabbit.
GLP compliance:
no
Remarks:
: older study, pre-dating mandatory GLP
Specific details on test material used for the study:
Pentaerythrite D (very finely ground), was available as a white powder. Charge no. 17.08.1982
Species:
rabbit
Strain:
other: white russian (albino)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Asta-Werke AG
- Age at study initiation: 10 months
- Weight at study initiation: 2.2-3.2kg
- Housing:stainless steel cage, Asta model
- Diet (e.g. ad libitum): standardised experimental animal feed Altromin
- Water (e.g. ad libitum):ad lib
- Acclimation period:1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1°C
- Humidity (%): 50-60%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):12


IN-LIFE DATES: From: To:
Type of coverage:
occlusive
Preparation of test site:
other: both abraded and intact skin were assessed
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g of the test material was dampened with 0.3 ml demineralised water.
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
3 females
Details on study design:
The back skin of the rabbits was shaved between the shoulder and crucial ligament region. The skin on the back of each rabbit was divided on both sides of the vertebral colum into 2 (a total of 4) areas. The contralateral areas were distinguished in that they consisted on the left side of intact skin, and on the right of scarified skin. The scarification was carried out superficially, avoiding more deep-seated defects and bleeding. Each of the 4 areas was covered with a piece of linen cloth approximately 6.25 cm² in size; 2 pieces of cloth were used to cover the applied test substance (one in the intact and one in the scarified region), sealed at suitable points in the untreated areas of skin. The linen cloth was adhered to a synthetic adhesive film. An occlusive bandage (Acrylastic, P. Beiersdorf and C.o. AG, Hamburg, no. 2408, width 8cm) was applied circularly around the body of the animal.

The patches were left in place for 4 hours. After removal of the bandage, skin reactions were scored at 1, 24, 48 and 72 hours later according to the Draize and OECD guidelines.

SCORING SYSTEM:
Erythema and scab formation
no erythema: 0; quite mild erythema (hardly perceptible): 1; clearly definable erythema: 2; moderate to severe erythema: 3; severe erythema (intense reddening) to mild scabbing (with deep-seated injury): 4

Oedema formation
no oedema: 0; quite mild oedema (hardly perceptible): 1; mild oedema (edges of the areas
well demarcated, marked swelling) :2; moderate oedema (swelling approx. 1 mm): 3;
intense oedema (swelling> 1 mm, extending beyond the point of application): 4

Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: No reaction at any time point (intact skin)
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: A theoretical assessment of the toxicokinetics of pentaerythritol indicates rapid and extensive absorption and distribution; rapid metabolism and excretipn are likley to limit systemic exposure and toxicity. No bioaccumulation is predicted.
Irritant / corrosive response data:
Erythema occurred neither on the intact nor on the scarified skin areas. The oedemas were of varying intensity. One hour after substance application both quite mild (evaluation stage 1) and intense oedema (evaluation stage 4) were observed on scarified skin only. These findings had already disappeared completely after 24 and 48 hours respectively.

No reactions were seen on intact skin at any time point.
Other effects:
Systemic-toxic effects did not occur after dermal application of the test product. The general health of the experimental animals was not affected.

No evidence of skin irritation was seen (inact skin).

Interpretation of results:
GHS criteria not met
Conclusions:
No evidence of irritation was seen on the intact skin sites; the substance is not classified as a skin irritant.
Executive summary:

The skin irritation properties of Pentaerythrite D (very finely ground) were evaluated in 3 female White Russian albino rabbits. 0.5 g of the moistened test substance was applied to the intact or scarified skin under an occlusive dressing. The dressing remained in place for 4 hours. After removal of the bandage, skin reactions were scored at 1, 24, 48 and 72 hours later according to the Draize and OECD guidelines. Systemic-toxic effects did not occur after dermal application of the test product. The general health of the experimental animals was not affected. No evidence of irritation was seen on the intact skin sites; the substance is not classified as a skin irritant.

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:
05 June to 24 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD guideline compliant study with no deviations
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
October 2012
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Pentaerythritol (chemical name 2,2-Bis(hydroxymethyl)-1,3-propanediol)
- Physical state: crystalline solid
- Analytical purity: 98.8%
- Lot/batch No.: 4410102701
- Expiration date of the lot/batch: 18 December 2016
- Storage condition of test material: ambient/dark
- pH: 4-7 at 20°C
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan UK, Oxon, England
- Age at study initiation: 12-15 weeks
- Weight at study initiation: 2.7-2.9 kg
- Housing: Individually in appropriately sized stainless steel cages with a ‘Noryl’ dual level interior and perforated floor. Beneath each cage was a suspended tray containing absorbent paper.
- Diet (e.g. ad libitum): Harlan diet ad libitum. Each animal was also offered a supplement of hay at least 3 times per week.
- Water (e.g. ad libitum): Water from the public supply ad libitum
- Acclimation period: up to 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (target 16-20°C)
- Humidity (%): 49% to 69% (target 40% to 70%)
- Air changes (per hr): at least 10 (100% fresh air)
- Photoperiod (hrs dark / hrs light): 12 hour cycle

IN-LIFE DATES: From: 08 July 2015 To: 23 July 2015
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye remained untreated to serve as a control
Amount / concentration applied:
The test substance was administered as supplied. The weight equivalent of 0.1 mL was determined at the Test Facility, and this weight was 84 mg.
Duration of treatment / exposure:
Not applicable - each animal received a single dose of the test substance, instilled into the lower conjunctival sac of the right eye. The lids were gently held closed together for 1-2 seconds.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing was not performed

SCORING SYSTEM: The scoring system detailed in OECD 405 (2012) was used; observations were made at 1, 4, 24, 48 and 72 hours after instillation.

TOOL USED TO ASSESS SCORE: hand-held magnifier and pen torch where necessary.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
There was no irritation noted at the cornea, iris or conjunctivae, and no ocular discharge was noted in either animal at any observation timepoint.
Other effects:
No other effects reported.

There was no irritation noted at the cornea, iris or conjunctivae, and no ocular discharge was noted in either animal at any observation timepoint. The mean values for each lesion, corneal opacity, iris, conjunctival redness and conjunctival chemosis were 0 (zero).

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not irritating to rabbit eyes and classification is not required.
Executive summary:

The eye irritation potential of pentaerythritol was evaluated in New Zealand White rabbits according to OECD Guideline 405. Two male rabbits were treated with the weight equivalent of 0.1 mL; determined to be 84 mg, of pentaerythritol, instilled into the lower conjunctival sac of the right eye. The left eye remained untreated and hence it acted as a control. Both eyes were examined for evidence of irritation approximately 1, 4, 24, 48 and 72 h after instillation. There was no irritation noted at the cornea, iris or conjunctivae, and no ocular discharge was noted in either animal at any observation timepoint. In conclusion, the instillation of pentaerythritol did not cause any ocular irritation to the rabbit eye. Based on the results of this study, pentaerythritol does not require classification for eye irritation according to CLP criteria.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

No evidence of irritant reactions was seen in on intact skin sites a guideline-comparable skin irritation study in the rabbit (Zechel, 1983).

Eye irritation

A recent GLP and guideline (OECD 405) compliant eye irritation study was conducted in the rabbit (Donald, 2015). A single instillation of pentaerythritol was made into the eye (weight equivalent of 0.1 mL) of two rabbits and reactions were recorded at 1, 4, 24, 48 and 72 hours later. There was no irritation noted at the cornea, iris or conjunctivae, and no ocular discharge was noted in either animal at any observation timepoint. Based on the lack of reactions observed, it was not necessary to test a third animal.

The results of an older study performed with pentaerythritol (Hercules, 1964) indicate that the substance is not an eye irritant, however this study is available as a secondary source only. The original study report is not available, however the results do not indicate any concerns for eye irritation.

Respiratory irritation

There is no evidence from worker exposure that the substance causes respiratory irritation.


Justification for selection of skin irritation / corrosion endpoint:
Single study available for this endpoint

Justification for selection of eye irritation endpoint:
Modern GLP and guideline compliant study

Justification for classification or non-classification

Based on the results of the available skin and eye irritation studies, no classification is required according to Regulation 1272/2008.