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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Published report of human patach testing performed with a number of latex additives.

Data source

Reference
Reference Type:
publication
Title:
Results of patch testing with a special series of rubber allergens
Author:
Holness DL & Nethercott JR
Year:
1996
Bibliographic source:
Contact Dermatitis 36: 207-211

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Human repeat insult patch test using a series of latex additive substances.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further details.
Specific details on test material used for the study:
4,4-dihydroxybiphenyl 0.1% was included in the 'special tray' of rubber chemicals for allergenicity patch testing, for comparison with a standard allergen tray.

Method

Type of population:
general
Ethical approval:
not specified
Subjects:
The main database consisted of 1670 patients who had been patch tested for allergic responses between 1981 and 1988 using either the European standard screening allergen tray (pre-1985) or the North American Contact Dermatitis Group standard screening tray (post-1985).
8.9% of this patient cohort had a positive response to at least one of the rubber components in the standard tray (typically thiuram mix, carba mix, black rubber mix, mercapto mix or mercaptobenzothiazole).

317 individuals from the original cohort of 1670 were identified and patch tested using the rubber tray - a series of rubber chemicals identified as potential allergens causing contact dermatitis or skin irritation. It is reported that the 317 individuals were more likely to be male, use gloves, have reported dermatitis on hands , feet and other general body areas, they were more likely to be health care workers. Although not explicitly stated it appears the cohort tested with the rubber tray had pre-existing contact dermatitis, probably associated with wearing latex gloves.
Clinical history:
- History of allergy for study subject or populations: No details other than indications that some of the 1670 patiets may have had existing allergic responses
- Symptoms, onset and progress of the disease: None provided in report

Controls:
The standard screening allergen tray was used as a control for the rubber chemicals allergen tray.
Route of administration:
dermal
Details on study design:
317 humans patch tested.
1670 patients were tested using a standard screening tray of allergens (the North American Contact Dermatitis Group standard screening tray), including a number of rubber components. 317 patients were also tested with a second tray of 27 specific rubber components.

Patients were tested using Al-test strips or Finn chambers. Strips were located on the dorsum and secured with Scanpor tape for a 2-3 day exposure period. Reactions were assessed 30-60 minutes after removal of the dressing and a second reading occurred 2-3 days later.
Reactions were assessed using the system of the International Contact Dermatitis Group.

The dermographic parameters used to analyse the results for patients exposed to the standard tray or standard and rubber trays, included age, past and family medical histories, daignosis, location of effect on body, job characteristics and use of protective gloves.

Results and discussion

Results of examinations:
The performance of the rubber tray was compared with standard allegen tray results. 4'4-dihydroxybiphenyl was not one of the substances involved in false-positive or false negative outcomes.

Human patch test response 2-3 days after challenge application -special rubber allergen tray - 0.1% concentrations used for dermal application.
1% of 311 exposed showed a positive response (three individuals). No clinical observations were reported associated with the response in the three sensitised individuals.

Of the original cohort of 1670 patients, 311 were tested with 4,4'-dihydroxybiphenyl as part of the rubber chemicals allergen series. The percent positive response was 1% or three individuals.
The results indicate that 4,4'-dihydroxybiphenyl has a very weak potential to elicit contact dermatitis in compromised patients. The tested cohort appears to be predominantly male, sensitised individuals with pre-existing allergic responses to latex gloves. The findings in the paper confirm that 4,4'-dihydroxybiphenyl may elicit an allergic or cross-reactivity response in individuals previously sensitised to rubber allergens.

Any other information on results incl. tables

Three individuals in the group of 311 subjects challenged with the 'rubber tray' showed a reaction to 4'4-dihydroxybiphenyl

Applicant's summary and conclusion

Conclusions:
1% of 311 human patch tests gave positive response, indicating that 4,4'-dihydroxybiphenyl may be a weak skin sensitiser.
Executive summary:

The study was designed to examine the results of patch testing with the rubber components on a standard allergenicity screening tray with the results from a special tray containing a series of 27 rubber components ("rubber tray") including 4,4'-dihydroxybipheny. 1670 patients were patch tested using the standard screening tray and then 317 of the original cohort were tested with the rubber tray. A low frequency of reactions (1%) was seen in the cohort of 317 patients tested with 4,4'-dihydroxybiphenyl.