Metam-sodium

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from European Food Safety Authority

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Conclusion regarding the peer review of the pesticide risk assessment of the active substance metam

Author:

European Food Safety Authority (EFSA)

Year:

2008

Bibliographic source:

EFSA Scientific Report (2008) 203, 1-97

Reference 2

Reference Type:

secondary source

Title:

Absorption, Distribution, Excretionand Metabolism study of 44-( Metam-sodium in mice and rat

Author:

Agriculture & Environment Research Unit (AERU)

Year:

2017

Bibliographic source:

Pesticide Properties Database (PPDB), Agriculture & Environment Research Unit (AERU), 14th Dec, 2017

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

In vivo Absorption, Distribution, Excretionand Metabolism study of 44-( Metam-sodium in mice and rat

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Metam-sodium

EC Number:

205-293-0

EC Name:

Metam-sodium

Cas Number:

137-42-8

Molecular formula:

C2H5NS2.Na

IUPAC Name:

sodium (methylcarbamothioyl)sulfanide

Details on test material:

SMILES:CNC(=S)S{-}.[Na]{+}

Specific details on test material used for the study:

- Name of test material (as cited in study report): Metam-sodium
- Molecular formula (if other than submission substance): C2H4NNaS2
- Molecular weight (if other than submission substance): 129.1826 g/mole
- Substance type: Organic

Radiolabelling:

not specified

Test animals

Species:

other: Mice and rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

not specified

Vehicle:

not specified

Details on exposure:

not specified

Duration and frequency of treatment / exposure:

not specified

Doses / concentrations

Remarks:

not specified

No. of animals per sex per dose / concentration:

not specified

Control animals:

not specified

Positive control reference chemical:

not specified

Details on study design:

not specified

Details on dosing and sampling:

not specified

Statistics:

not specified

Results and discussion

Preliminary studies:

not specified

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Oral absorption of metam is rapid and almost complete (85%) based on urinary and expired air excretion (50 and 35%, respectively).

Main ADME results 2

Type:

distribution

Results:

Metam is uniformly distributed with slight accumulation in the thyroid in mice and rats

Main ADME results 3

Type:

metabolism

Results:

The metabolism of metam is extensive and rapid, suggesting a decomposition of metam into MITC, CO2, and COS. MITC is further conjugated to glutathione and excreted in urine while CO2 and COS are excreted via expired air.

Main ADME results 4

Type:

excretion

Results:

Excretion is almost complete within 24-48 h after administration, with minor portions excreted up to 168 h after dosing.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral absorption of metam is rapid and almost complete (85%) based on urinary and expired air excretion (50 and 35%, respectively).

Details on distribution in tissues:

Metam is uniformly distributed with slight accumulation in the thyroid in mice and rats

Details on excretion:

Excretion is almost complete within 24-48 h after administration, with minor portions excreted up to 168 h after dosing.

Metabolite characterisation studies

Metabolites identified:

yes

Remarks:

MITC, CO2, and COS. MITC, CS2

Details on metabolites:

The metabolism of metam is extensive and rapid, suggesting a decomposition of metam into MITC, CO2, and COS. MITC is further conjugated to glutathione and excreted in urine while CO2 and COS are excreted via expired air. The other significant pathway for metam is the release of CS2, which could be related to the acidic conditions existent in the stomach of the rat (pH=3.8-5) following oral ingestion.

Applicant's summary and conclusion

Conclusions:

Low bio-accumulation potential based on study results

Executive summary:

Available data pertaining to the in-vivo Absorption,Distribution, Metabolism and Excretion of the chemical 4-(Metam-sodium suggests absorbed Orally rapid and almost complete (85%) based on urinary and expired air excretion (50 and 35%, respectively) and uniformly distributed with slight accumulation in the thyroid in mice and rats. The metabolism of metam is extensive and rapid, suggesting a decomposition of metam into MITC, CO2, and COS. MITC is further conjugated to glutathione and excreted in urine while CO2 and COS are excreted via expired air. The other significant pathway for metam is the release of CS2, which could be related to the acidic conditions existent in the stomach of the rat (pH=3.8-5) following oral ingestion. Excretion is almost complete within 24-48 h after administration, with minor portions excreted up to 168 h after dosing.Thus, there is low evidence of4-(Metam-sodiumto accumulate in tissues and cause a concern for consumer safety. Also, th use as a pesticide, plant fumigant to control weeds, nematodes, fungi, bacteria and insects (United states environment protaction agecny, 1994). Hence it is concluded that Metam-sodiumis likely to exhibit low bio-accumulation potential based on study results and use.