Zinc bis(N-ethyl-N-phenyldithiocarbamate)

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and sufficient documented

Objective of study:

metabolism

Principles of method if other than guideline:

After oral administration of 1000 mg/kg of ZEPC to Wistar rats female rats, the metabolites in the blood were extracted with ethyl acetate.

GLP compliance:

no

Specific details on test material used for the study:

No data.

Radiolabelling:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

No data

Duration and frequency of treatment / exposure:

No data

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

No data

Control animals:

not specified

Positive control reference chemical:

No data

Details on study design:

Metabolites in the blood were extracted with ethyl acetate and identified by GC-MS.

Type:

metabolism

Results:

N-ethylaniline and Aniline were identified as metabolites

Details on absorption:

No data

Details on distribution in tissues:

No data

Details on excretion:

No data

Metabolites identified:

yes

Details on metabolites:

N-ethylaniline and Aniline were identified as metabolites.

Conclusions:

N-ethylaniline and Aniline were idetified as metabolites.

Executive summary:

After oral adminisatration of 1000 mg/kg of ZEPC to Wistar rats female rats, the metabolites in the blood were extracted with ethyl acetate. N-ethylaniline (N-EA) and Aniline (AN) were identified as metabolites. N-EA and AN concentrations in the blood reached maximum levels (10.0 and 2.01 µg/ml) after 24 hr and then decreased to less than 0.3 µg/ml within 3 days. The increased methemoglobin levels in the blood after administration of ZEPC were nearly proportional to the changes in blood concentrations.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and sufficient documented

Objective of study:

toxicokinetics

Principles of method if other than guideline:

To 4 groups of rats, 5-6 weeks old, a mixture of radioactive labelled zinc ethylphenyldithiocarbamate was administered orally by gavage. After 3, 6, 24 and 72 hours blood, faeces, urine as well as liver, lungs, spleen, kidneys and fatty tissue were examined for radioactivity.

GLP compliance:

no

Specific details on test material used for the study:

14C labelled zinc ethylphenyldithiocarbamate was used.

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Duration and frequency of treatment / exposure:

single application

Dose / conc.:

688.5 mg/kg bw (total dose)

Remarks:

266.5 mg ladiolabbeled (14C) and 422 mg unlabelled inc ethylphenylditiocarbamate/kg bw

No. of animals per sex per dose / concentration:

4 groups of 5 rats each/dose

Control animals:

not specified

Positive control reference chemical:

None

Details on dosing and sampling:

After 3, 6, 24 and 72 hours bllod, faeces, urin aswell as liver, lungs, spleen, kidneys and fatty tissue were examined for radioactivity.

Type:

absorption

Results:

As 25% of radioactivity was excreted via urine, it was also inferred that 25-40% of administered zinc ethylphenyldithiocarbamate was absorbed via gastro intestinal tract.

Details on absorption:

The percentage of excretion into faeces was about 60% in 24 hr and about 65% in 72 hr, while that into urine was about 15% in 24 hr and about 25% in 72 hr. As 25% of radioactivity was excreted via urine, it was also inferred that 25-40% of administered zinc ethylphenyldithiocarbamate was absorbed via gastro intestinal tract.

Details on distribution in tissues:

All organs and tissues examined showed the highest radioactivity 3 - 6 hours after the oral administration and the radioactivity declined with time. In the early stage after the administration, the radioactivity was highest in the blood, followed by the liver and kidney. Although the radioactivity decreased with time, the liver and kidney still showed higher levels after 24 hr than other organs and tissues.

Test no.:

#1

Transfer type:

other:

Observation:

other: All organs and tissues examined showed the highest radioactivity 3 - 6 hours after the oral administration and the radioactivity declined with time.

Test no.:

#1

Toxicokinetic parameters:

other: At the beginning, the radioactivity was highest in the blood, followed by the liver and kidney. Although the radioactivity decreased with time, the liver and kidney still showed higher levels after 24 hr than other organs and tissues.

Metabolites identified:

yes

Details on metabolites:

In the urine N-ethylaniline, aniline and p-acetoaminophenol were found as metabolites.

Conclusions:

About 25-40% of administered zinc ethylphenyldithiocarbamate was absorbed via gastro intestinal tract. In the early stage after the administration, the radioactivity was highest in the blood, followed by the liver and kidney. Although the radioactivity decreased with time, the liver and kidney still showed higher levels after 24 hr than other organs and tissues. In the urine N-ethylaniline, aniline and p-acetoaminophenol were found as metabolites.

Executive summary:

To 4 groups of rats, 5-6 weeks old, a mixture of radioactive labelled zinc ethylphenyldithiocarbamate was administered orally by gavage. After 3, 6, 24 and 72 hours blood, faeces, urine as well as liver, lungs, spleen, kidneys and fatty tissue were examined for radioactivity.

The percentage of excretion into faeces was about 60% in 24 hr and about 65% in 72 hr, while that into urine was about 15% in 24 hr and about 25% in 72 hr. As 25% of radioactivity was excreted via urine, it was also inferred that 25-40% of administered zinc ethylphenyldithiocarbamate was absorbed via gastro intestinal tract. All organs and tissues examined showed the highest radioactivity 3 - 6 hours after the oral administration and the radioactivity declined with time. In the early stage after the administration, the radioactivity was highest in the blood, followed by the liver and kidney. Although the radioactivity decreased with time, the liver and kidney still showed higher levels after 24 hr than other organs and tissues. In the urine N-ethylaniline, aniline and p-acetoaminophenol were found as metabolites.

Description of key information

In a toxicokinetik study to 4 groups of rats, 5-6 weeks old, a mixture of radioactive labelled zinc ethylphenyldithiocarbamate was administered orally by gavage. After 3, 6, 24 and 72 hours blood, faeces, urine as well as liver, lungs, spleen, kidneys and fatty tissue were examined for radioactivity. The percentage of excretion into faeces was about 60% in 24 hr and about 65% in 72 hr, while that into urine was about 15% in 24 hr and about 25% in 72 hr. As 25% of radioactivity was excreted via urine, it was also inferred that 25-40% of administered zinc ethylphenyldithiocarbamate was absorbed via gastro intestinal tract. All organs and tissues examined showed the highest radioactivity 3 - 6 hours after the oral administration and the radioactivity declined with time. In the early stage after the administration, the radioactivity was highest in the blood, followed by the liver and kidney. Although the radioactivity decreased with time, the liver and kidney still showed higher levels after 24 hr than other organs and tissues. In the urine N-ethylaniline, aniline and p-acetoaminophenol were found as metabolites.

In another study, after oral administration of 1000 mg/kg of ZEPC to Wistar rats female rats, the metabolites in the blood were extracted with ethyl acetate. N-ethylaniline (N-EA) and aniline (AN) were identified as metabolites. N-EA and AN concentrations in the blood reached maximum levels (10.0 and 2.01 µg/ml) after 24 hr and then decreased to less than 0.3 µg/ml within 3 days. The increased methemoglobin levels in the blood after administration of ZEPC were nearly proportional to the changes in blood concentrations.

For zinc ethylphenyldithiocarbamate a reaction to the carcinogenic ethylphenylnitrosamine can be expected with nitrosating agents. Technical products can be contaminated with the respective nitrosamines (Toxicological evaluations of the BG Chemie for zinc ethylphenyldithiocarbamate No. 219 in German).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential