Registration Dossier

Administrative data

Description of key information

Human cases have shown that contact dermatitis patients, for whom a rubber intolerance was often present, occasionally reacted positively to 1,3-diphenylguanidine in the patch test. Taken into account the negative Guinea pig maximisation assay, it can be infer that the positive reactions observed in human patients with contact dermatitis reflected cross-reactions rather than a direct sensitising effect of 1,3-diphenyl guanidine.

Additional information

In persons suffering from a contact dermatitis positive 1,3-diphenylguanidine patch tests have occasionally been described (see the following table). The following main contact possibilities were named: shoes (Blank & Miller, 1952; de Vries, 1964; Hjorth & Fregert, 1972; Song et al., 1979; Lynde et al., 1982; Bajaj et al., 1988), articles of clothing (Bandmann, 1956; van Dijk, 1968; Song et al., 1979), rubberized protective clothing (Fegeler, 1963; Götz & Istvanovic, 1963; Höfer & Hänemann, 1967; Ross & Obst, 1969) and other rubber articles, e.g. gloves or the rubber parts of milking machines (Nater, 1975; Song et al., 1979).

A tire production employee, whose allergic rhinitis symptoms occurred only at the workplace, had a positive patch test reaction with 1% 1,3-diphenylguanidine (Camarasa & Alomar, 1978).

Garcia-Perez et al.(1984) found that Spanish agricultural workers with a contact dermatitis had a significantly higher sensitization to 1,3-diphenylguanidine than a contact dermatitis control group working in another profession (11.76% versus 5.32%). The authors attributed this to possible cross-reactions with pesticides, as some of these substances (e.g. Cyprex) are guanidine derivatives and others (e.g. the cyanamides) possess a similar chemical structure.

The available data are summarised in the following table.

Results of Patch Tests Performed with 1,3-diphenylguanidine

Subjects (n)

Positive(n)

+ve reaction (%)

Concentration (%)

Reference

35

2

6

1

Adams, 1972

524

6

0.01

1+2.1

Agrup, 1969

1

1

-

1

Aguirre et al., 1994

229

18

8

0.5

Baer et al., 1973

105

3

3

3

Bajaj et al., 1988

5

1

20

1

Bandmann, 1956

24

0

0

1

Blank & Miller, 1952

74

2

3

 n. g. *

Bonnevie & Marcussen, 1944

1

1

-

n. g.

Bruze, 1994

1

1

-

1

Calan, 1978

686

13

2.3

n. g.

Conde-Salazar et al., 1993

5

0

0

0.25

Curtis, 1945

59

0

 

1

Dahl, 1975

9

1

11

n. g

de Vries, 1964

34

4

12

n. g.

Garcia-Perez et al., 1984

244

13

5

n. g.

Garcia-Perez et al., 1984

17

6

35

1

Götz & Istvanovic, 1963

1

1

-

n. g.

Helander & Mäkelä, 1983

63

15

24

n. g

Herrmann & Schulz, 1960

10

3

30

n. g.

Höfer & Hönemann, 1967

316

14

4.4

1

Holness and Nethercott, 1997

20

7

35

n. g.

Jung, 1977

5

1

20

1

Kanerva et al., 1994

11

0

0

1

Kanerva et al., 1996

31

2

7

1

Kantoh et al., 1985

46

4

8.7

1

Kiec-Swierczynska, 1995

50

2

4

n. g.

Kilpikari, 1982

15

0

0

1

Knudsen et al., 1993

30

1

3.3

1

Koch et al., 1996

1

0

-

1

Koch, 1996

61

2

3

1

Lisi & Simonetti, 1985

61

3

5

1

Lisi & Simonetti, 1985

119

3

3

1

Lynde et al., 1982

1377

5

0.4

n. g.

Meneghini et al., 1963

49

2

4

70

Monsanto, 1982

6

2

33

1

Nater, 1975

n. g.

n. g.

3****

n. g.

Orlov et al., 1973

5

4

80

n. g.

Piskin et al., 2006

844

44

5

1

Rajan & Khoo, 1980

1600

25

1.6

1

Reifferscheid, 1979

2

0

-

n. g.

Roed-Petersen & Menne, 1976

15

1

7

1+2

Ross & Obst, 1969

744

74***

9.9

1

Rudzki & Kleniewska, 1970

47

6

l3

n. g.

Rudzki & Kohutnicki, 1971

1

1

-

n. g.

Ruocco & Florio, 1986

50

6

12

1

Saha et al.; 1993

502

7

1.4

2

Suskind, 1984

4

3

75

n. g

Takeda et al., 1964

32

0

0

1

te Lintum & Nater, 1973

1

0

-

1

Tuyp & Mitchell, 1983

3

1

33

2

van Dijk, 1968

106

-**

-

1

Wilson, 1969

* n. g. = not given

** no evaluation possible due to a number of irritating reactions

*** possible irritating reactions could not be ruled out

**** scarification of skin