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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
other: published data
Adequacy of study:
supporting 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:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 427 (Skin Absorption: In Vivo Method)
Deviations:
yes
Remarks:
Recovery was not in the required range. Volatile 14C-compounds were not collected.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: compact
Details on test material:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
- Name of test material (as cited in study report): Ziram
- Lot no.: 027F9221
- Purity: 96.9%
Radiolabelling:
yes
Remarks:
(14C)-Ziram

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
- Source: Charles River Laboratories, Wilmington, Massachusetts, US
- Weight: 237-267 g (Individual data of control group not reported)

Administration / exposure

Type of coverage:
open
Vehicle:
water
Duration of exposure:
0.5, 1, 2, 4, 10 and 24 h
Doses:
1.2, 9.9, 57.1% (w/v)
No. of animals per group:
4 per timepoint
Control animals:
yes

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
not examined
Absorption in different matrices:
see Table 6_2-1
Total recovery:
see Table 6_2-1
Percutaneous absorptionopen allclose all
Dose:
0.086 mg/cm²
Parameter:
percentage
Absorption:
28.5 %
Remarks on result:
other: 24 h
Dose:
0.95 mg/cm²
Parameter:
percentage
Absorption:
30.7 %
Remarks on result:
other: 24 h
Dose:
7.25 mg/cm²
Parameter:
percentage
Absorption:
4.89 %
Remarks on result:
other: 24 h

Any other information on results incl. tables

Table A6_2-1:     Mean recovery of radioactivity from male rats following a single dermal application of (14C)-ziram

Parameter /Tissue

1.07 mg/rat

11.9 mg/rat

90.6 mg/rat

[%] of administered dose

0.5 h

1 h

2 h

4 h

10 h

24 h

0.5 h

1 h

2 h

4 h

10 h

24 h

0.5 h

1 h

2 h

4 h

10 h

24 h

Skin rinse

75.22

85.35

78.90

74.64

70.07

70.53

72.39

69.03

67.03

60.71

72.33

68.79

101.96

99.79

99.73

97.20

100.26

93.49

Skin cell cover

   0.06

   0.08

   0.12

   0.12

   0.26

   0.60

   0.02

   0.04

   0.05

   0.06

   0.14

   0.16

   0.04

   0.06

   0.18

   0.26

   0.15

   0.35

Skin enclosure

   0.10

   0.14

   0.33

   0.20

   0.07

   0.35

   0.42

   0.17

   0.31

   0.17

   0.09

   0.43

   1.02

   1.44

   1.02

   0.22

   1.03

   1.26

Total nonabsorbed dose

75.38

85.57

79.35

74.96

70.40

71.48

72.83

69.24

67.39

60.94

72.56

69.38

103.02

101.29

100.93

97.68

101.44

95.10

Urine

ND

ND

0.01a

0.02

0.06a

0.16

ND

ND

0.01

0.01

0.02

0.05

ND

ND

ND

0.01

0.01

0.01

Faeces

ND

ND/NS

ND

ND/NS

ND

0.01

ND/NS

ND/NS

ND/NS

ND/NS

ND/NS

0.01a

ND/NS

0.01c

ND/NS

ND/NS

ND/NS

ND

Cage wash

ND

ND

ND

ND

ND

0.02b

ND

ND

   0.01c

ND

ND

ND

ND

ND

ND

ND

ND

ND

Cage wipe

ND

ND

0.01a

0.01

0.01

0.01

ND

0.01c

0.01c

0.01b

0.01

0.01

0.01c

0.01b

ND

0.01b

ND

0.01b

Total excreted

ND

ND

0.01

0.02

0.06

0.18

ND

0.01

   0.01

0.01

0.02

0.05

0.01

0.01

ND

0.01

0.01

0.01

Carcass

ND

ND

ND

ND

0.08

0.14

ND

ND

0.01

ND

ND

0.03

ND

ND

ND

ND

ND

ND

Skin

5.63

3.18

4.57

5.05

7.88

3.79

3.04

3.48

5.67

9.93

8.86

4.46

0.56

0.93

1.11

1.48

1.44

1.52

Total absorbed dose

5.63

3.18

4.57

5.07

8.02

4.11

3.04

3.48

5.68

9.93

8.88

4.54

0.56

0.93

1.11

1.48

1.44

1.52

Total recovery

81.01

88.75

83.92

80.03

78.42

75.59

75.87

72.72

73.07

70.87

81.44

73.92

103.58

102.22

102.04

99.16

102.88

96.62

NS    Not sampled

ND   Not detectable

a      Mean of three animals

b      Mean of two animals

c      Mean of one animal

 

 

 

Table A6_2-2:     Concentations of radioactivity in blood from male rats following a single dermal application of (14C)-ziram

 

Dose level

µg ziram/g

0.5 h

1 h

2 h

4 h

10 h

24 h

1.07 mg

0.002

ND

ND

ND

0.002

0.006

.006

11.9 mg

ND

ND

ND

ND

ND

ND

90.6 mg

ND

ND

ND

ND

ND

ND

ND    Not detectable

 

Applicant's summary and conclusion

Conclusions:
Dithiocarbamates are related compounds to xanthates and xanthate esters. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2
Less than 0.3% of the administered radiolabel was retained in the carcass and was eliminated in the excreta within 24 h after exposure.
The mean amount absorbed (sum of radiolabel in urine, carcass, and skin at the test site) by 24 h was 29% of the administered dose in animals at 1.1 mg, 31% in those at 12 mg, and 5% for those at 91 mg, indicating non-linear dermal absorption.
Executive summary:

Less than 0.3% of the administered radiolabel was retained in the carcass and was eliminated in the excreta within 24 h after exposure. The mean amount absorbed (sum of radiolabel in urine, carcass, and skin at the test site) by 24 h was 29% of the administered dose in animals at 1.1 mg, 31% in those at 12 mg, and 5% for those at 91 mg, indicating non-linear dermal absorption.