Ziram

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Mar 1988 - 03 Aug 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Recovery was not in the required range.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Version / remarks:

not specified

Deviations:

yes

Remarks:

Recovery was not in the required range. Volatile 14C-compounds were not collected.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ziram

EC Number:

205-288-3

EC Name:

Ziram

Cas Number:

137-30-4

Molecular formula:

C6H12N2S4Zn

IUPAC Name:

ziram

Radiolabelling:

yes

Remarks:

(14C)-labelled

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:

1.1, 12 and 91 mg/animal corresponding to 0.086, 0.95 and 7.25 mg/cm², respectively

No. of animals per group:

4/dose/time point

Control animals:

yes

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

not examined

Absorption in different matrices:

The mean absorption values (sum of dose in urine, carcass, skin at the application site and nonaccountable) at 24 h were 28.5, 30.7 and 4.89% for the 1.1, 12 and 91 mg/animal doses respectively. For details, please refer to Table 1 under "Any other information in results incl. tables".

Total recovery:

The mean total recoveries were 81.28, 74.63 and 101.1%, for the 1.1, 12 and 91 mg/animal doses respectively. For details, please refer to Table 1 under "Any other information in results incl. tables".

Percutaneous absorption

Percutaneous absorption 1

Key result

Time point:

24 h

Concentrate / Dilution:

dilution

Dose:

0.086 mg/cm²

Parameter:

percentage

Absorption:

28.5 %

Percutaneous absorption 2

Key result

Time point:

24 h

Concentrate / Dilution:

dilution

Dose:

0.95 mg/cm²

Parameter:

percentage

Absorption:

30.7 %

Percutaneous absorption 3

Key result

Time point:

24 h

Concentrate / Dilution:

dilution

Dose:

7.25 mg/cm²

Parameter:

percentage

Absorption:

4.89 %

Any other information on results incl. tables

Table 1:    Mean recovery of radioactivity from male rats following a single dermal application of (^14C)-labelled test substance
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 2:    Concentations of radioactivity in blood from male rats following a single dermal application of (^14C)-labelled test substance
Dose level	µg test substance/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:

The study was conduct according to GLP and similar to OECD guideline 427. Following topical application of 0.086, 0.95 and 7.25 mg/cm² of the 14C-labelled test material formulated as wettable powder to male rats, the total absorbed dose was 28.5, 30.7 and 4.89% of the applied dose, respectively after 24 h.