Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Developmental study of Metam-sodium in Rats
Author:
Linda L. Carlock
Year:
2001
Bibliographic source:
Handbook of Pesticide Toxicology, Chapter 87, Volume 2.2001
Reference Type:
secondary source
Title:
Metam-sodium: developmental toxicity study in rats
Author:
US EPA
Year:
1994
Bibliographic source:
United states environment protaction agecny, 1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
Teratology study of Metam-sodium in Rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
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

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
- Source: Barriered animal breeding unit at Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: An aqueous solution of metam sodium (42.2%) was administered at 0, 5, 20 and 60 mg/kg by gavage to pregnant Wistar rats
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Details on mating procedure:
not specified
Duration of treatment / exposure:
11 days
Frequency of treatment:
Daily
Duration of test:
Days 6-12 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
5 mg/kg bw/day
Dose / conc.:
20 mg/kg bw/day
Dose / conc.:
60 mg/kg bw/day
No. of animals per sex per dose:
not specified
Control animals:
yes, concurrent vehicle
Details on study design:
not specified

Examinations

Maternal examinations:
Clinical signs, body weight gain, food consumption and food efficiency were examined.
Ovaries and uterine content:
Not specified
Fetal examinations:
Fetal weights, Gross pathology and histopathology was examined.
Statistics:
Not specified
Indices:
Not specified
Historical control data:
Not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
When treated wtih 20 and 60 mg/kg/day, Piloerection, salivation, and urinary incontinence were observed in treated rats.

When treated wtih 5 mg/kg/day, No clinical signs were observed in treated rats.
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
When treated wtih 20 and 60 mg/kg/day, decreased in body weight gain was observed in treated female rats as compared to control.

When treated wtih 5 mg/kg/day, marginal decreased in body weight gain was observed in treated female rats as compared to control.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
When treated wtih 20 and 60 mg/kg/day, decreased in food consumption was observed in treated female rats as compared to control.

When treated wtih 5 mg/kg/day, marginal decreased in food consumption was observed in treated female rats as compared to control.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
Remarks on result:
other: No effect observed

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
When treated wtih 20 and 60 mg/kg/day, decrease in fetal weight were observed as compared to control.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
effects observed, treatment-related
Description (incidence and severity):
When treated wtih 20 and 60 mg/kg/day, reduced ossification of manus and pes were observed in fetus of treated rats.
Skeletal malformations:
effects observed, treatment-related
Description (incidence and severity):
When treated wtih 20 and 60 mg/kg/day, increased incidences of minor skeletal defects and/or variants were observed in fetus of treated rats.
Visceral malformations:
not specified
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
external malformations
skeletal malformations
Remarks on result:
other: No effect observed

Fetal abnormalities

Abnormalities:
not specified
Description (incidence and severity):
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 5 mg/kg/day for P and F1 generation when Wistar female rats were treated with Metam-sodium orally by gavage on Days 6-17 of gestation.
Executive summary:

In a deelopmental toxicity study, Wistar male and female rats were treated with Metam-sodium in the concentration of 0, 5, 20 and 60 mg/kg/day by gavage on Days 6-17 of gestation. Piloerection, salivation, and urinary incontinence were observed in treated rats at 20 and 60 mg/kg/day. No clinical signs were observed in treated rats at 5 mg/kg/day. Decreased in body weight gain and food consumption was observed in treated female rats at 20 and 60 mg/kg/day as compared to control. Similarly, Marginal decreased in body weight gain and food consumption was observed in treated female rats at 5 mg/kg/day as compared to control. In addition, decrease in fetal weight, reduced ossification of manus and pes and increased incidences of minor skeletal defects and/or variants were observed in fetus of treated rats was observed at 20 and 60 mg/kg/day as compared to control. Therefore, NOAEL was considered to be 5 mg/kg/day for P and F1 generation when Wistar female rats were treated with Metam-sodium orally by gavage on Days 6-17 of gestation.