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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Results of epidemiologic study, published in peer-reviewed literature, minor restrictions in reporting, but otherwise adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Skin-sensitizing and irritant properties of propylene glycol
Author:
Lessmann H, Schnuch A, Geier J, Uter W
Year:
2005
Bibliographic source:
Contact Dermatitis, 53, 247-259

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
skin sensitisation
Principles of method if other than guideline:
Patients with suspected allergic contact eczema, attending the contact allergy clinics comprising the multicenter project, were patch tested with the standard series of the German Contact Dermatitis Research Group (DKG). Patch tests were performed in accordance with current DKG guidelines and international recommendations. Patch test material was applied for 24 or 48 hours, readings were taken until at least 72 hr, using the following gradings: neg, ?, +, ++, +++, irritant and follicular. In total, patch test data of 45183 patients who have been tested with 20% monopropylene glycol in water between 1992 and 2002 were analysed.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
other: patients with suspected allergic contact eczema
Details on study design:
HYPOTHESIS TESTED: skin irritating and sensitizing properties of monopropylene glycol


METHOD OF DATA COLLECTION
- Type: Clinical tests
- Details: Patients with suspected allergic contact eczema, attending the contact allergy clinics comprising the multicenter project, were patch tested with the stadard series of the German Contact Dermatitis Research Group (DKG). Patch tests were performed in accordance with current DKG guidelines and international recommendations. Patch test material was applied for 24 or 48 hours, readings were taken until at least 72 hr, using the following gradings: neg, ?, +, ++, +++, irritant and follicular. The patch results of every reading, a standardized history (comprising age, sex, atopic diseases, current and former occupation)s) and presumptive causal exposures), as well as final diagnosis and site of dermatitis were assessed and documented. All data were regularly transferred to the data center in Göttingen in an anonymized format. Frequencies of sensitization (as percentage of patients tested) were calculated as crude proportions and as proportions standardized for sex and age, following current guidelines. The RI and the PR were calculated as further parameters to assess the diagnostic quality of a patch test preparation.
For comparison of the demographic characteristic of patients positive and non-positive to an allergen, the MOAHLFA index was used. With the positive versus non-positive patch test reaction as outcome, a Poisson regression analyss is performed, quantifying the independent impact of the MOAHLFA factors on PG-sensitization risk by the prevalence ratio, accompanied by 95% confidence intervals. Further information from the patient history, particularly the occupation of allergic and non-allergic patch test patients, was considered.


STUDY PERIOD: from 1992 to 2002


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): not reported
- Selection criteria: patients tested with monopropylene glycol additionally to the standard series between 1992 and 2002
- Total number of subjects participating in study: 45138
- Sex/age/race: 28928 females and 16210 males


HEALTH EFFECTS STUDIED
- Disease(s): allergic contact eczema
Details on exposure:
TYPE OF EXPOSURE: dermal

EXPOSURE PERIOD: 24 or 48 hours


POSTEXPOSURE PERIOD: at least 72 hours


DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: neg, ?, +, ++, +++, irritant and follicular
Statistical methods:
SAS 8.2 (SAS Institute, Cary, NC, USA)

Results and discussion

Results:
FINDINGS
Out of 45138 patients, 1044 (2.3%, 32 females and 412 males) tested positively: 895 patients with a 1+ (2.0%), 129 patients with a 2+ (0.3%) and 20 patients (0.04%) with a 3+ reaction. In addition, 1083 doubtful, follicular or erythematous reactions (2.4%) and 271 explicitly irritant reactions (0.6%) have been observed. Of the 895 1+ reactions, 114 (12.7%) were singular reactions to monopropylene glycol without any concomitant reaction to other substances. The RI was -0.14 and the PR 85.7%.
Regarding the MOAHLFA index, there were only little differences between patients with positive reactions and those with negative reactions to monopropylene glycol. The greatest difference was the high portion (27.2% versus 13.1%) of patients with leg dermatitis, which turned out to be the only significant risk factor, about doubling the risk of monopropylene glycol sensitization. The frequencies of hand and face dermatitis in monopropylene glycol-positive patients were lower than that in patch-test-negative patients. In accordance with the unremarkable proportion of occupation-related cases there were no distinctly different patterns of occupations in monopropylene glycol-positive versus monopropylene glycol-negative patients. With the exception of topical therapeutics, which have been quoted more frequently in the monopropylene glycol-sensitive group (43.0% versus 32.7% in the control group), no difference was found between the 2 groups (monopropylene glycol-positive versus monopropylene glycol-negative) with regard to the frequencies of the suspected causative exposures.
Confounding factors:
In 396 cases cofactors have been deemed to contribute to the skin reactions; in 166 of these cases (41.9% versus 19.4% in the control group), chronic venous deficiency has been noted. The association of a positive reaction to monopropylene glycol with leg dermatitis can also be shown by Poisson regression analysis and the resulting prevalence ration of 2.10.
Analysing the pattern of concomitantly positive patch test reactions to other allergens in monopropylene glycol-positive versus -negative patients, high (age andsex-standardized) frequencies of concomitant reactions to the fragrance mix (31.0% versus 12.1%), Myroxylon pereirae resin (balsam of Peru; 27.8% versus 9.3%), lanolin alcohol (17.2% versus 4.6%), Amerchol L-101 (16.9% versus 4.8%), colophony (14.3% versus 4.2%), methyldibromo glutaronitrile/phenoxyethanol (1:4) (9.8% versus 3.7%), cetearyl alcohol (8/0% versus 1.2%), neomycine sulfate (6.8% versus 2.7%) and several other allergens, including potentially irritant patch test preparations such as phenyl mercucy acetate (14.5% versus 6.5) or cocamidopropyl betaine (11.1% versus 2.1%) were found.

Applicant's summary and conclusion