Reaction mass of ethanol and propan-2-ol

Endpoint summary

Description of key information

Ethanol:
Skin irritation: Not irritating
Eye irritation: Irritating
Isopropanol
Skin irritation studies on isopropyl alcohol in rabbits and guinea pigs have demonstrated that the compound is not a skin irritant. 
Eye irritation studies on isopropyl alcohol in rabbits have demonstrated that the compound is an eye irritant.  

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

There are no data available for the reaction mass. Based on data for the two constituents the reaction mass is considered to be not irritating to skin but irritating to the eye.

Ethanol:

SKIN IRRITATION

In a guideline skin irritation study using rabbits, ethanol caused mild transient irritation (very slight, barely perceptible erythema) which disappeared within 48 hours of application. In a study that was similar to the Draize protocol for skin irritancy testing, rabbits were exposed to liquid ethanol for a period of 24 hours under occlusive conditions. Only slight irritation was seen, only marginally worse than was also seen in the distilled water control. As observations were only made for 24 hours, reversibility could not be assessed.

In a study that was designed to be as similar as possible to the Draize protocol for skin irritancy testing, human male volunteers were exposed to liquid ethanol for a period of 24 hours under occlusive conditions, using the forearm as the site of exposure. In a study that was designed to assess the potential for skin irritation under severe repeated dose conditions, ethanol was applied under occlusive conditions to the skin (backs) of male human volunteers. The application was repeated daily and the response checked from the previous dose before each fresh application. No irritation was seen until day 13, after which the irritative response slowly increased, initially as erythema until by day 19 erythema plus induration were also seen. The study was halted on day 21. Up to 4 -hour covered skin patch tests were conducted in 31 volunteers using 0.2 ml neat ethanol. A reaction determined to be indicative of irritation (+ or greater, on a scale of 0, +, ++, or +++) was seen in just one individual. 15 of the 31 volunteers reacted to similar patches with 20% sodium dodecyl sulfate (SDS). Irritation was assessed in a study of skin condition following the repeated "in use" application of ethanol-containing gels for hand disinfection. The forearm skin of 13 female volunteers was treated every 20 minues, for 6 consecutive hours, with five gels containing between 70 - 80% ethanol. There was no evidence of skin irritation for any of the gels when the application sites were assessed 1 or 24 hour following the treatments. A sensorial evaluation of the same gels was conducted in 21 (18 female; 3 male) professional health-care workers, with long experience of using such alcohol-base rubs. In each case, 3 ml product was rubbed into both hands for 30 seconds. Although there were several reports of redness and/or irritation amongst these professionals for the two gels containing 75% or 80% ethanol, the investigators considered that these were likely to result from pre-existing irritated and damaged skin

Overall, the results indicate that ethanol has a low potential to irritate the skin of humans under anything other than extreme and unrealistic exposure conditions

EYE IRRITATION

In a reference handbook of peer reviewed, guideline GLP eye irritation study results in rabbits, ethanol was found to cause eye irritation. All symptoms reversed within 14 days. The response was not sufficiently severe to trigger classification under the criteria of directive 67/548 but was sufficient with respect to the corneal and conjunctival effects to trigger classification as a reversible eye irritant (category 2) under the EU GHS regulation. In a guideline eye irritation study results in rabbits for which only basic but key details are reported, ethanol was found to cause eye irritation. The response was not sufficiently severe to trigger classification under the criteria of directive 67/548 but, based on the available information, appears to be sufficient with respect to the corneal and conjunctival effects to trigger classification as an eye irritant (category 2) under the EU GHS regulation. The study did not include sufficient observations to be able to judge reversibility. In an eye irritation study which was carried out according to guideline but for which only very basic results are available, ethanol was found to cause marked eye irritation in rabbits. The detail of the results was insufficient to establish whether the substance should be classified as an eye irritant or not. The study also examined the impact of washing on the severity of the response seen. These clearly showed that rinsing after exposure decreases the immediate acute response slightly but dramatically decreases the length of time for which effects persist.

Isopropanol:

Skin irritation:

 

Isopropyl alcohol did not induce dermal irritation in intact and abraded skin of rabbits or guinea pigs after a single 4-hour occlusive application. A skin irritation study on isopropyl alcohol has been performed in accordance with revised Federal Hazardous Substances Act (FHSA) procedure that had been proposed by the FDA (Nixonet al., 1975).  In this study, rabbits (strain and number of animals not reported) and Hartley guinea pigs (number of animals not reported) wereexposedto isopropyl alcohol (vehicle not reported) on the intact and abraded sites (total number of sites tested was 6 for intact skin and 6 for abraded skin) under occlusive conditions.  Animals were exposed to the test compound for 4 hours and observations were recorded at 4, 24, and 48 hoursafter removal of the patch(washing not reported).   Skin reactions were scored according to a prescribed numerical system (Edwards, 1972) and the primary irritation indice (PII) was calculated by averaging the scores for all test sites.  In addition, tissue destruction was presented as the number of sites that showed tissue destruction or a reaction grade >4.0, excluding actual abrasion, at any grading time and as a function of the total number of sites tested. 

In both rabbits and guinea pigs, the mean score for irritant response was 0 for both intact and abraded skin. The PII was 0 and the tissue destruction fraction was 0 out of 6, whether the skin was intact or abraded. Based on the results of this study, isopropyl alcohol is not a skin irritant.Isopropyl alcohol is not classified as a skin irritant according to the CLP classification criteria. 

Eye Irritation:

 

Eye irritation studies on isopropyl alcohol in rabbits have demonstrated that the compound is an eye irritant. 

An eye irritation study on isopropyl alcohol has been performed in rabbits (Plutnick, 1986).  In this study, 0.1 mL of undiluted isopropyl alcohol was instilled into one conjunctival sac of each of 6 New Zealand White rabbits (3/sex).  Ocular changes were assessed 1, 4, 24, 48, 72 hours and 4, 7, 10, and 14 days after treatment, and scoring was performed according to the guideline methods with additional parameters assessed for the conjunctivae and cornea.  Instillation of isopropyl alcohol caused conjunctival, corneal, and iridial responses in all animals. Conjunctival responses, including redness, chemosis, and clear/white discharge were observed in all animals 1 hour after treatment. Specificially, redness was noted in all animals from 1 hour after treatment through to Day 10. Although the incidence of redness was observed to be decreased at study termination (Day 14), redness was still noted in 3 animals. Chemosis was noted in all animals from 1 hour through to 48 hours after treatment. The incidence of chemosis decreased afterwords and chemosis was not noted on Day 14. Clear and/or white discharge was noted in all animals at the 1 and 4 hour observations and was fully reversed by Day 4. Conjunctival ulceration was noted in 5 animals during the study. Iridial responses were noted in all animals during the study and were reversed by Day 7. Corneal responses including, opacity and stippling, were observed in 5 animals. Corneal ulceration was noted in all animals. Corneal responses in all animals were reversed by Day 7. Other observations noted during the study included dye retentionof the nictitating membrane and conjunctiva and conjunctival blistering. Ocular irritation was most prominent from 1 hour after treatment through to Day 4. The total Draize score ranged from 4 to 25. Three of the 6 rabbits displayed conjunctival redness on Day 14. Under the conditions of this study, isopropyl alcohol was considered to be irritating to rabbit eyes. 

According to CLP classification criteria, isopropyl alcohol is classified ascategory II (causes serious eye irritation).

 

In another eye irritation study conducted with rabbits (Eye Irritation: Reference chemicals data bank, 1998), undiluted isopropyl alcohol was instilled into 4 rabbits (strain not reported), and ocular changes were assessed 24, 48, 72 hours and 7 and 10 days after treatment. Ocular changes were scored against the maximum average scoring system of Draize (1944). The modified maximum average scored at 1 day was 30.5 out of a possible score of 110. Effects were fully reversed in 10 days. Therefore, isopropyl alcohol is irritating to rabbit eyes. 

According to CLP classification criteria, isopropyl alcohol is classified ascategory II (causes serious eye irritation).

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on data for the two constituents the reaction mass does not need to be classified for skin irritation according to DSD or CLP, but does need classification for eye irritation (R36 according to DSD and H319 according to CLP).

Ethanol:

The degree of skin irritation reponse is insufficient to warrant labelling as a skin irritant either under directive 67/548 or the EU GHS regulation. Direct comparison of the results against the EU classification criteria is not possible, but the slight response seen coupled with the similar response seen with distilled water strongly suggest that this substance will not meet the criteria for classification as a skin irritant and that it has minimal skin irritation potential. No irritation was seen, supporting the case that ethanol does not warrant classification as a skin irritant. The results indicate that ethanol has, at most, just a very low potential to irritate the skin of humans.

There is clear evidence that ethanol is an eye irritant. From the data available however, there is no need for classification under the criteria of directive 67/548. The table below shows a summary of the end point responses assessed in the two available guideline studies and how they compare to the classification criteria for this directive:

Testing of pure ethanol. Classification triggered for effects seen under directive 67/548

Study	Iritis	Corneal effects	Conjunctival redness	Chemosis
ECETOC	No	No	No	No
Jacobs	No	No	No	No

However, the data shows that the irritation response is sufficiently severe with respect to a number of end points to trigger classification as a reversible eye irritant (category 2) under the EU regulation 1272/2008, because of the more severe criteria (lower thresholds of effects triggering classification). The results per study and per end point are shown in the table below:

Testing of pure ethanol. Classification triggered for effects seen under regulation 1272/2008

*=just meets threshold.

It is quite clear that the conjunctival effects trigger classification, in this case as a reversible eye irritant (cat 2, H319) even without taking into account the fact that in 3 of the 5 studies, corneal effects were severe enough to trigger classification. 

Isopropanol

 Skin irritation: The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.

Eye irritation: according to CLP calssifcation criteria, the substance does meet the criteria for classification and labelling for this endpoint (category II: causes serious eye irritation) as set out in Regulation (EC) No. 1272/2008.