Sodium O-isobutyl dithiocarbonate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium 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

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

Test material information

Constituent 1

Reference substance name:

Ziram

EC Number:

205-288-3

EC Name:

Ziram

Cas Number:

137-30-4

IUPAC Name:

zinc bis(dimethyldithiocarbamate)

Test material form:

solid: compact

Details on test material:

Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium 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 or test system 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 absorption

Percutaneous absorption 1

Dose:

0.086 mg/cm²

Parameter:

percentage

Absorption:

28.5 %

Remarks on result:

other: 24 h

Percutaneous absorption 2

Dose:

0.95 mg/cm²

Parameter:

percentage

Absorption:

30.7 %

Remarks on result:

other: 24 h

Percutaneous absorption 3

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	0.01^a	0.02	0.06^a	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	0.01^a	ND/NS	0.01^c	ND/NS	ND/NS	ND/NS	ND
Cage wash	ND	ND	ND	ND	ND	0.02^b	ND	ND	0.01^c	ND	ND	ND	ND	ND	ND	ND	ND	ND
Cage wipe	ND	ND	0.01^a	0.01	0.01	0.01	ND	0.01^c	0.01^c	0.01^b	0.01	0.01	0.01^c	0.01^b	ND	0.01^b	ND	0.01^b
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. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium 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.