1-o-tolylbiguanide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Tests on Humans

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Company report outlining positive effects on workers.
Although not a formal clinical study, the information is considered sufficient for classification as Skin Sens 1

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Human survey done, survey is limited to the effects experienced by those who have been exposed to OTB directly or indirectly at the Consett site of Thomas Swan & Co. Ltd.

GLP compliance:

no

Type of study:

other: human experience

Justification for non-LLNA method:

Human survey done, survey is limited to the effects experienced by those who have been exposed to OTB directly or indirectly at the Consett site of Thomas Swan & Co. Ltd.

Test material

Test material information

Constituent 1

Reference substance name:

1-o-tolylbiguanide

EC Number:

202-268-6

EC Name:

1-o-tolylbiguanide

Cas Number:

93-69-6

Molecular formula:

C9H13N5

IUPAC Name:

1-o-tolylbiguanide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

In vivo test system

Test animals

Species:

other: Human

Study design: in vivo (non-LLNA)

Induction

Adequacy of induction:

other: Human observations - workers

Challenge

Adequacy of challenge:

other: Human observations - workers

No. of animals per dose:

19 workers assessed, of whom, several reported adverse effects

Results and discussion

In vivo (non-LLNA)

Results

No. with + reactions:

11

Total no. in group:

19

Clinical observations:

industrial dermatitis

Remarks on result:

positive indication of skin sensitisation

Remarks:

industrial dermatitis

Any other information on results incl. tables

In all but one case, dermatitis occured only after a period of time. All of those affected described the problem as beginning in the "sweaty" areas of the skin e.g around the edges of a dust mask or on the wrist underneath a cuff. Symptoms displayed were, itchiness accompanied by tiny blisters underneath the skin surface followed by the formation of keens and skin loss.

The individual operators used the same level of personal protection throughout their stay in this plant - so a change in level of protection does not seem to be a factor in their eventual development of dermatitis. Therefore the skin problems must have occured because either: -

1) the operators became careless regarding their personal protection or

2) sensitisation to the product developed over a period of time.

If 1) then the dermatitis should have cleared up when they resumed their normal level of care. However, in all cases the skin condition persisted until the operators were removed from the plant. This suggests that sensitisation did take place and that a low level of exposure experienced when wearing the protective equipment was now sufficient to cause an allergic reaction, whereas, previously, the same level of exposure had caused no problems.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

On balance, the historical evidence suggests that Casamine OTB may be a skin sensitiser rather than simply an irritant.

Executive summary:

Animal testing cannot be justified on the basis of human data