Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
other: human data
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
other: Any kind of reliability rating is not considered to be applicable, since human epidemiological studies, field studies and case reports are not conducted/reported according to standardised guidelines
Rationale for reliability incl. deficiencies:
other: publication with methodological deficiencies

Data source

Reference
Reference Type:
publication
Title:
Allergic contact sensitization to the toluic acids
Author:
Emmett, E.A. et al.
Year:
1973
Bibliographic source:
The Journal Of Investigative Dermatology, Vol. 61, No. 5, 282-285

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:
The objective of the study was to assess the sensitising potential of toluic acids by a procedure according to Draize with modifications. Two experiments were conducted with 25 healthy human volunteers. Two experiments were conducted. In experiment A, 10 subjects were exposed simultaneously to p-toluic acid and o-toluic acid (both 50 % in polystyrene) for induction. After induction phase, m-,o-, and p-toluic acids (50 % in polystyrene, 5 % and 1 % in petrolatum) were tested separately for its ability to elicit sensitisation. Reactions were recorded and scored 48, 96 and 144 hours after elicitation exposure. In experiment B, 15 subjects were exposed to o-toluic acid (50 % in polystyrene). After induction phase, o-, and p-toluic acids (50 % in polystyrene, 5 % and 1 % in petrolatum) as well as m-toluic acid (5 % and 1 % in petrolatum) were tested separately for its ability to elicit sensitisation. Reactions were recorded and scored 48 and 96 hours after elicitation exposure.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- toluic acids were pulverised before mixing with solvents (polystyrene or petrolatum)

Method

Type of population:
general
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: 25
- Sex: 14 males and 11 females
- Age: 19 - 49 years
- Race: 23 Caucasians and 2 Negroes
Clinical history:
- History of allergy or casuistics for study subject or populations:
None of the subjects gave a past history suggestive of atopy or of contact sensitivity, apart from seasonal poison ivy dermatitis
Controls:
10 subjects were patch tested for a single 48 hour application to ensure that concentrations were nonirritating
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
Patch testing was performed according to Draize method with modifications. A small quantity of each test material was placed on a wetted (tap water) central gauze portion of a Johnson & Johnson 1.5-inch-square BandAid before application to a nonhairy region of the upper back. Strips of Dermicel hypoallergenic tape were used to occlude, cover and secure patches. Patches were applied on 3 days per week for 3 weeks (in total 9 applications) and left in place for 24 hours. Residual test material was removed with soft pads wetted with either water or 70 % alcohol. Challenge application was performed in the 6th week by application of patches to a previously untested area of the skin of the upper back using the same method of application described above except they were left in place for 48 hours.


EXAMINATIONS
- Grading/Scoring system: readings were performed on days 1, 3, 5, 8, 10, 12, 15, 17, 19 and 22 (induction phase), as well as on days 36, 38, 40 and 42 (elicitation phase). Grading of reactions was performed using the scale recommended by the International Contact dermatitis League* as follows: negative reactions, doubtful reactions, weak (nonvesicular) reactions, strong (edematous or vesicular) reactions and extreme reactions.

*Reference:
Wilkinson DS, Fregert S, Magnusson B, Bandmann HJ, Calnan CD, Cronin E, Hjorth N, Maibach HJ, Malten KE, Meneghini CL, Pirila V: Terminology of contact dermatitis. Acta Derm Venerol (Stockh) 50: 287-293, 1970

Results and discussion

Results of examinations:
Experiment A: Reactions were observed in all 4 subjects after induction with m-toluic acid (50 % in polystyrene), which were previously sensitised with p- and o-toluic acid (50 % in polystyrene). In 3 of 4 subjects a reaction was also observed after induction with m-toluic acid (5 % in petrolatum). No reactions were observed after induction with m-toluic acid (1 % in petrolatum)
Experiment B: Reactions were observed in 2 of 6 subjects on day 37 and in 3 of 6 subjects on day 38 after induction with m-toluic acid (5 % in petrolatum), which were previously sensitised with o-toluic acid (50 % in polystyrene). No reactions were observed after induction with m-toluic acid (1 % in petrolatum)

Applicant's summary and conclusion

Conclusions:
Two experiments were conducted, assessing the potential to induce sensitisation (o-and p-toluic acid) and the potential to elicit a sensitisation reaction (o-, p- and m-toluic acid)
Experiment A: Reactions were observed in all 4 subjects after induction with m-toluic acid (50 % in polystyrene), which were previously sensitised with p- and o-toluic acid (50 % in polystyrene). In 3 of 4 subjects a reaction was also observed after induction with m-toluic acid (5 % in petrolatum). No reactions were observed after induction with m-toluic acid (1 % in petrolatum)
Experiment B: Reactions were observed in 2 of 6 subjects on day 37 and in 3 of 6 subjects on day 38 after induction with m-toluic acid (5 % in petrolatum), which were previously sensitised with o-toluic acid (50 % in polystyrene). No reactions were observed after induction with m-toluic acid (1 % in petrolatum)

No conclusion can be drawn from the above publication due to lack of quality, reliability and adequacy of the experimental data for the fulfilment of data requirements under REACH.

The references represents human data on sensitisation with very limited value for risk assessment purposes, since the potential of m-toluic acid to induce sensitisation was not assessed. The reference does not fulfil the criteria for quality, reliability and adequacy of experimental data for the fulfilment of data requirements under REACH and hazard assessment purposes (ECHA guidance R4 in conjunction with regulation (EC) 1907/2006, Annexes VII-X).