2-methylpentane-2,4-diol

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Skin reactions to hexylene glycol

Author:

Kinnunen T. & Hannuksela M.

Year:

1989

Bibliographic source:

Contact Dermatitis; 21: 154-158

Materials and methods

Type of sensitisation studied:

skin

Study type:

survey

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Hexylene glycol at 50% or 30% in water was patch tested in eczema patients subjected to routine patch testing to examine any irritant or sensitizing properties. The effects of hexylene glycol on transepidermal water loss (TEWL), skin blood flow were also examined.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpentane-2,4-diol

EC Number:

203-489-0

EC Name:

2-methylpentane-2,4-diol

Cas Number:

107-41-5

Molecular formula:

C6H14O2

IUPAC Name:

2-methylpentane-2,4-diol

Details on test material:

- Name of test material (as cited in study report): hexylene glycol
- Physical state: liquid

Method

Type of population:

other: patients suspected to have allergic contact dermatitis

Ethical approval:

not specified

Subjects:

- Number of subjects exposed: 823 (423 patients with 50% hexylene glycol in water and 400 patients with 30% hexylene glycol in water)
- Sex: male/female

Clinical history:

- Known diseases: dermatitis

Route of administration:

dermal

Results and discussion

Results of examinations:

A study conducted in 823 eczema patients reported that hexylene glycol used in patch testing (48 hour occlusive) at aqueous concentrations of 30 or 50% caused oedema and erythema of the skin in 2.8% of the patients tested (Kinnunen & Hannuksela, 1989). The authors considered this indicative of irritation due to application of hexylene glycol.

Any other information on results incl. tables

Oedema and erythema reactions to 30% or 50% HG in ordinary patch tests occurred in 2.8% of the patients subjected to routine patch testing (Table 1). The corresponding result for 30% PG was 3.8%. HG caused erythema in only 5.7% of the patients, PG in 7.4%. The capacity of 50% HG to produce some kind of reaction in patch tests equalled that of 30% PG, as can be seen in Table 1.

Patch testing with dilution series of HG and PG (30, 10, 2 and 1% glycols in water) was performed on 22 patients with an erythema and oedema reaction to 30% of either glycol (Table 2). 1 patient, a 35-year-old man, was negative to 50% HG and positive to 1% PG. On the other band, all 3 patients showing a positive patch test reaction to 1-2% HG were positive to 30% PG but not to lower concentrations.

The 2 patients with a positive patch test reaction to 1% HG were subjected to ROATs, one with 5% and the other with 30% HG in water. Both ROATs remained negative. 4 other patients with a positive patch test response to 30% HG. but not to lower concentrations, were ROAT-negative to 30% HG and 5% PG. 1 patient, a 66-year-old woman, had a severe eczema on her feet and lower legs. In the European standard patch test series, neomycin and fragrance-mix were clearly positive. In additional patch tests, 30% PG and 50% HG were strongly positive (3+). ROAT both with 5% PG and with 30% HG became positive on the 3rd day. Unfortunately, patch tests with dilution series were not done.

PG, but not HG, significantly increased the TEWL in 3 days among the atopics and in 8 days among the non-atopics. In NIICRs to 250 mM BA, no differences were seen between the skin areas treated with the glycols and the untreated control skin.

After 24 h occlusion, the TEWL from PG was the highest. Next in order were HG and filter paper disc without any glycol. The order of substances in LDF measurements was the same as for TEWL except for the empty chamber, under which the blood flow was at about the same level as for HG but clearly lower than for PG.

Table 1.Patch test reactions to 30% propylene glycol (PG)and to 30% and 50% hexylene glycol (HG) in 823 patch-tested eczema patients.

(a). Comparison of 30% PG and 50% HG in 423 patients

	Reaction to 50% HG in water
Reaction to 30% PG in water	++,+	?+	-
	No	No	No
++,+	3	1	6
?+	1	3	26
-	3	24	356

(b) Comparison of 30% PG and 30% HG in 400 patients

	Reaction of 30° o HG in water
Reaction to 30% PG in water	++,+	?+	-
	No	No	No
++,+	9	2	10
?+	3	3	20
-	4	14	335

Occlusion time: 48 h. Results read 96 h after application. + + =erythema, oedema and vesicles; + = erythema and oedema; ?+ =erythema only: - = negative.   Table 2. 48 h patch test reactions to dilution series of hexylene glycol (HG) and propylene glycol (PG) in water; the lowest concentrations of each glycol giving and erythema and oedema reaction are indicated in the table.

	HG negative to	HG positive to
PG	30%	30%	10%	2%	1%
-ve to 30%	-	4	0	0	0
+ve to 30%	8	4	0	1	2
+ve to 10%	0	2	0	0	0
+ve to 2%	0	0	0	0	0
+ve to 1%	1	0	0	0	0

Applicant's summary and conclusion

Executive summary:

The irritant and sensitizing properties of HG have been studied in eczema patients. Swelling and redness were seen in 23 out of 823 (2.8%) eczema patients who were treated with a 30% or 50% aqueous solution in a 48-hr covered patch test. In 48-hr covered patch tests, two of 23 eczema patients reacted to a 1% aqueous solution. As this concentration was substantially lower than that at which healthy subjects or eczema patients generally experience irritation, it was suspected that these two patients might be showing allergic reactions. However, neither reacted to twice daily uncovered exposures to hexylene glycol (5% in one patient, 30% in the other) for 7 days. Another patient who had responded strongly to a 48-hr covered patch test with 50% aqueous hexylene glycol also reacted to repeated applications of a 30% aqueous solution. The investigators were unable to draw firm conclusions as to the nature of the reactions in these three patients.

. In patch tests with dilution series, 2 patients reacted to 1% HG, but in both cases ROAT with HG rernained negative. One other patient with a 3+ patch test reaction to 50% HG had a positive ROAT result to 30% HG in water. HG did not increase transepidermal water loss both in atopic normal-looking skin and among healthy controls. The present results suggest that HG is less irritating than PG under occlusion, but that delayed contact allergic reactions may occur.

Swelling and redness were seen in 23 out of 823 eczema patients who were treated with a 30% or 50% aqueous solution in a 48-hr covered patch test