Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404, rabbit, RA to CAS 38172-91-7): not irritating (BASF, 1987)
Eye irritation (OECD 405, rabbit, RA to CAS 38172-91-7) serious eye damage (Categorie 1). The substance has to be classified with R41 (BASF, 1987)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions, Source substance for RA information according to analogue justification.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Weight at study initiation: male (mean) = 2.63 Kg, female = 2.54 Kg
- Housing: stainless steel cages (40 x 51 cm) with wire mesh walk floors, one animal per cage, no bedding, saw-dust in waste trays
- Diet (e.g. ad libitum): 130g per animal per day
- Water (e.g. ad libitum): 250ml tap water per animal per day
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animals
Amount / concentration applied:
0.5 ml undiluted test substance
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 (2 males, 1 female)
Details on study design:
TEST SITE
- Area of exposure: upper third of the back or flank
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: test patches were secured with four layers of absorbent gauze and a porous bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 4 hours washed with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 72 hours

SCORING SYSTEM: as described in OECD 404 test guideline
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Reversibility:
other: no signs of irritation were observed
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Reversibility:
other: no edema was observed

The test substance did not cause any edema or erythema except of one male which developed a very slight erythema extending beyond the area of exposure after 4 hours which was fully reversible within 20 hours.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification: not irritating
Executive summary:

According to OECD 404, skin irritation was tested without GLP compliance. The applicant site of 2,5 x 2,5cm of 3 white Vienna rabbits was exposed for 4h to undiluted test item using semiocclusiv conditions and washed with Lutrol and Lutrol/water (1:1) followed by a 72 hours observation period with readings after 30 min and 60 min after the removal of the test patches and 24 h, 48 h and 72 h after the beginning of application. Untreated skin sites of the same animal were used as negative control.

No signs of irriation or corrosion were observed at any time. Based on this study, the test substance could be classified as non irritating. (BASF, 1987)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions, Source substance for RA information according to analogue justification.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Offenbach/Main, Germany
- Weight at study initiation: male (mean) = 3.02 Kg, female = 2.60 Kg
- Housing: stainless steel cages (40 x 51 cm) with wire mesh walk floors, one animal per cage, no bedding, saw-dust in waste trays
- Diet (e.g. ad libitum): 130g per animal per day
- Water (e.g. ad libitum): 250ml tap water per animal per day
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eyes of the same animals
Amount / concentration applied:
0.1 ml undiluted test substance
Duration of treatment / exposure:
single application
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 (2 males, 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 21 days

SCORING SYSTEM: as described in test guideline
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0.2
Reversibility:
not fully reversible within: 21 days in 1/3 animals
Remarks on result:
other: mean score 0.0 in 2/3 animals; mean score 0.7 in 1/3 animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Remarks on result:
other: no effects in 3/3 animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
1.6
Reversibility:
not fully reversible within: 21 days in 1/3 animals
Remarks on result:
other: mean score 2.0 in 1/3 animals; 1.0 in 1/3 animals; 1.7 in 1/3 animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0.4
Reversibility:
not fully reversible within: 21 days in 1/3 animals
Remarks on result:
other: mean score 0.0 in 2/3 animals; mean score 1.3 in 1/3 animals

The severity of substance induced eye effects was quantified for each time point using the following values:

Cornea/Opacity

Conjunctivae/ Redness

Iris

Chemosis/Swelling

0 = none

0 = normal

0 = normal

0 = none

1 = very slight

1 = slight

1 = circum-corneal injection

1 = very slight

2 = well-defined

2 = well-defined

2 = iritis

2 = well-defined

3 = moderate to severe

3 = severe

 

3 = moderate to severe

4 = severe to very severe

 

 

4 = severe to very severe

The irritation scores were calculated as mean of the single values of the time points 24 h, 48 h and 72 h and all three animals.

Cornea score/Opacity

0.2

Conjunctivae score/Redness

1.6

Iris score

0.0

Chemosis score/Swelling

0.4

One male animal showed contracted pupils starting 48 hours after application until day 21. Eight days after application of the test substance this animal also developed small retractions in the eyelid, loss of corneal tissue and suppuration. These effects persisted unchanged until day 21. Furthermore this animal showed marginal vascularization of the cornea on day 21 while the second male did not show any of these effects at any time point. The female developed loss of corneal tissue and contracted pupils only 48 hours after application of the test substance. These effects were fully reversible within 24 hours.

Based on the irreversible effects in one animal the test substance hold the risk of serious eye damage.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information GHS Criteria used for interpretation of results: EU
Conclusions:
irreversible eye effects, risk of serious damage to eyes
Executive summary:

A single application of 0.1 ml of the unchanged test substance was given into the conjunctival sac of the right eyelid of 3 white vienna rabbits without GLP compliance according to OECD 405 . Eye effects were documented 1 h, 24 h, 48 h, 72 h, 8 days, 15 days and 21 days after the application and the untreated eyes were used as negative control.

One male animal showed not reversible effects after day 21, while the second male did not show any of these effects at any time point. The female developed loss of corneal tissue and contracted pupils only 48 hours after application of the test substance. These effects were fully reversible.

Based on the irreversible effects in one animal the test substance hold the risk of serious eye damage and should be classified as eye irritating category 1 (GHS). (BASF, 1987).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

 

 

Substance

Skin/Eye irritation

Target substance

2-Propyn-1-ol, polymer with ethylene oxide

(CAS 25749-64-8)

Skin: not irritating (RL3)

Eye: different results (RL3)

·        irritating

·        severe eye damage

Source substance (RA)

2-Propyn-1-ol, compd. with methyloxirane

(CAS 38172-91-7)

Skin: not irritating (RL2); approx. 50%

Eye: severe eye damage (RL2); approx. 50%

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2-Propyn-1-ol, polymer with ethylene oxide (CAS# 25749-64-8).

 

Since only less reliable studies investigating the skin and eye irritation are available for 2-Propyn-1-ol, polymer with ethylene oxide(CAS 25749-64-8),a read-across from the structurally related analogue substance2-Propyn-1-ol, compd. with methyloxirane (CAS 38172-91-7) was usedin accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5.

 

Skin

 

Non-OECD Guideline studies:

         a)     Target substance (2-Propyn-1-ol, polymer with ethylene oxide)

 

Before OECD Guideline 404 was established, skin irritation was tested using an internal method. 2 white vienna rabbits were treated for 1, 5 and 15 minutes and for 20h using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance and effects on skin were observed after 4h, 1,4,6 and 7 days after patch removal. There was no corrosion or irritation at any time. Based on this study, the test substance could be classified as non-irritating (BASF, 1977).

b)     Target substance (2-Propyn-1-ol, polymer with ethylene oxide)

Before OECD Guideline 404 was established, skin irritation was tested using an internal method. 2 white vienna rabbits were treated for 1, 5 and 15 minutes and for 20 hours using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance and effects on skin were observed after 4h, 1,4,6 and 7 days after patch removal. Directly after patch removal, there were effects visible for erythema 0.25 for both animals. There were slight effects 24h after patch removal for animal 1 and no effects for animal 2. There was no corrosion at any time. Based on this study, the test substance could be classified as non-irritating (BASF, 1975).

OECD guideline study:

 

a)     Source substance:2-Propyn-1-ol, compd. with methyloxirane (CAS 38172-91-7) (Read across)

 

According to OECD 404, skin irritation was tested without GLP compliance. The applicant site of 2.5 x 2.5cm of 3 white Vienna rabbits was exposed for 4h to undiluted (but a.i. approx. 50%) test item using semiocclusiv conditions and washed with Lutrol and Lutrol/water (1:1) followed by a 72 hours observation period with readings after 30 min and 60 min after the removal of the test patches and 24 h, 48 h and 72 h after the beginning of application. Untreated skin sites of the same animal were used as negative control. No signs of irritation or corrosion were observed at any time. Based on this study, the test substance could be classified as non-irritating (BASF, 1987).

Eye

Non-OECD Guideline studies:

 

a)     Target substance (2-Propyn-1-ol, polymer with ethylene oxide)

 

White Vienna rabbits were used and 50µl of the test substance were applied to the conjunctival sac of one eye of 2 animals. The saline-treated adjacent eye served as a control. The eyes were not washed out after 24h. The animals were observed 8 days whereupon changes were recorded after 10 minutes, 1h, 3h and on day 1,3,6 and 8.

The report describes mean scoring (24h/72h) for the following findings:

- cornea: 1.25

- iris: 0.5

- conjunctiva: 1.75

- chemosis: 2.0

 All effects were not fully reversible after 8 days, beside iris effects. It is important to keep in mind, that the substance is not washed out. Next to the effects described above, there is a scar formation visible after 72h, which is not reversible (BASF, 1977).

b)     Target substance (2-Propyn-1-ol, polymer with ethylene oxide)

White Vienna rabbits were used. 50µl of the test substance were applied to the conjunctival sac of one eye of 2 animals. The saline-treated adjacent eye served as a control. The eyes were not washed out after 24h. The animals were observed 8 days whereupon changes were recorded after 10 minutes, 1h, 3h and on day 1,2,5,7 and 8. The report describes findings after 1hour with scoring 1 for conjunctiva redness, scoring 2 for chemosis but no opacity of cornea. After 24h, there is scoring 1 for conjunctiva redness, scoring 1.5 for chemosis and scoring 1 for opacity of cornea. All effects were fully reversible and after 8 days, there were no effects detectable. It is important to keep in mind, that questionable effects in raw data were transferred to slight effects, for example in redness, in summary. Based on this study, the test substance showed moderately irritating effects (BASF, 1975).

OECD guideline study:

 

c)     Source substance:2-Propyn-1-ol, compd. with methyloxirane (CAS 38172-91-7) (Read across)

 

A single application of 0.1 ml of the unchanged test substance was given into the conjunctiva sac of the right eyelid of 3 white vienna rabbits without GLP compliance according to OECD 405. Eye effects were documented 1 h, 24 h, 48 h, 72 h, 8 days, 15 days and 21 days after the application and the untreated eyes were used as negative control. One male animal showed not reversible effects after day 21, while the second male did not show any of these effects at any time point. The female developed loss of corneal tissue and contracted pupils only 48 hours after application of the test substance. These effects were fully reversible. Based on irreversible effects in one animal, the test substance holds the risk of serious eye damage. (BASF, 1987)

Key study assignment:

 

Skin:

There are few information according skin irritation available. For the target substance the available studies (BASF 1975, 1977), are not so well documented and thus judged as less reliable, especially as the studies are not more critical than the study conducted with the source substance which has a lower purity. Therefore further information from a study of source substance (BASF, 1987) with higher reliability can be assigned as key study underlining a homogenous skin irriation behaviour and less reliable information was assigned as supporting studies.

 

Eye:

There are few information according eye irritation available. For the target substance the available studies (BASF 1975, 1977), are not so well documented and thus judged as less reliable especially as the studies are not more critical than the study conducted with the source substance which was conducted with a lower concentrated test item. All information show a nearly homogenous pictures of eye irriation with servere irriating effects, therefore further information from a study of source substance (BASF, 1987) with higher reliability was assigned as key study and less reliable information was assigned as supporting studies.

 

Conclusions

 

Skin:

In summary, two less reliable skin irritation studies from 2-Propyn-1-ol, polymer with ethylene oxide(CAS 25749-64-8) are available which points to no skin irritation. Another reliable skin irritation study from source substance (read across substance, lower purity) 2-Propyn-1-ol, compd. with ethyloxirane (CAS 38172-91-7), which showed no skin irritation, was used to assess the irritation potential. Source as well as target substance shows a similar behavior, therefore toxicological similarity is assumed and information from source subsance is used as key information.

Based on results mentioned above, the substance should not be classified as skin irritating.

 

Eye:

In summary, two less reliable eye irritation studies from 2-Propyn-1-ol, polymer with ethylene oxide(CAS 25749-64-8) areavailable which points to moderate irritation (BASF, 1975) and severe eye damage (category 1) (BASF, 1977). Another reliable eye irritation study from source substance (read across substance, lower purity) 2-Propyn-1-ol, compd. with methyloxirane (CAS 38172-91-7), which showed severe eye damage is available.

Source as well as target substance shows a similar behavior, therefore toxicological similarity is assumed and information from source subsance is used as key information.

Based on results mentioned above, the substance should be classified as severe eye damaging (category 1), following the most critical finding.

 

In summary the available data for a close homologue source substance and the target substance itself indicate no skin irritation, but severe eye damage. 



Justification for selection of skin irritation / corrosion endpoint:
Worst case study.

Justification for selection of eye irritation endpoint:
Worst case study.

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to Regulation (EC) 1272/2008 the substance is classified as

-         Skin irritation: not classified

-         Eye irritation: category 1 (H318)