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EC number: 205-293-0 | CAS number: 137-42-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
NOAEL was considered to be 11.5mg/kg/day for male and 13.5 mg/kg/day female for P and F1 generation when Alpk: Apf SD male and female rats were treated with Metam-sodium orally by gavage for in drinking water for 65 days and more days.
Thus, based on the above studies on Metam-sodium, it can be concluded that Metam-sodium is toxic to reproduction till dose of 13.5 mg/kg bw. Thus, comparing this effect with the criteria of CLP regulation, Metam-sodium can be classified under “category II” for reproductive toxicity.
Thought, the test substance Metam-sodium is classified under category II, Metam-sodium is extensive and rapidly metabolize 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. Hence, Metam-sodium is show Low bio-accumulation potential. The ADI proposed by the RMS in the DAR was 0.001 (EFSA Scientific Report (2008) 203, 1-97) and Metam-sodium is use as a pesticide, plant fumigant to control weeds, nematodes, fungi, bacteria and insects (United states environment protaction agecny, 1994). Hence, Metam-sodium is considered to be of no safety concern.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from secondary source
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Multigeneration reproduction study of Metam-sodium in Rats
- GLP compliance:
- not specified
- Limit test:
- no
- 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 - Species:
- rat
- Strain:
- other: Alpk: Apf SD
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Barriered animal breeding unit at Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: (P) x wks; (F1) x wks: 10 weeks - Route of administration:
- oral: drinking water
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- water
- Remarks:
- drinking
- Details on exposure:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): drinking water
- Concentration in vehicle: 0, 1.2, 3.2 and 11.5 mg/kg/day for males and 0, 1.8, 3.9 and 13.5 mg/kg/day for females. - Details on mating procedure:
- Details on study schedule
- F1 parental animals not mated until [...] weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were [...] days of age.
- Age at mating of the mated animals in the study: [...] weeks
(Explain how study was performed on perents and offspring separately whatever information we have) At 21 days of age, pups from the parental (F0) generation
were selected as parents for the F1 generation.
- M/F ratio per cage: 1:1 - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 65 days and more
- Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 1.2 mg/kg bw/day
- Remarks:
- for male
- Dose / conc.:
- 3.2 mg/kg bw/day
- Remarks:
- for male
- Dose / conc.:
- 11.5 mg/kg bw/day
- Remarks:
- for male
- Dose / conc.:
- 1.8 mg/kg bw/day
- Remarks:
- for female
- Dose / conc.:
- 3.9 mg/kg bw/day
- Remarks:
- for female
- Dose / conc.:
- 13.5 mg/kg bw/day
- Remarks:
- for female
- No. of animals per sex per dose:
- Total: 240
0 (vehicle) mg/kg/day: 30 male, 30 female
1.2 mg/kg/day: 30 male
3.2 mg/kg/day: 30 male
11.5 mg/kg/day: 30 male
1.8 mg/kg/day: 30 female
3.9 mg/kg/day: 30 female
13.5 mg/kg/day: 30 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Not specified
- Positive control:
- Not specified
- Parental animals: Observations and examinations:
- Survival, Clinical sign, Body weight and weight gain, food consumption and water consumption were examined.
- Oestrous cyclicity (parental animals):
- Not specified
- Sperm parameters (parental animals):
- Not specified
- Litter observations:
- Clinical sign and Body weights sex were examined.
- Postmortem examinations (parental animals):
- Gross pathology and histopathology was examined
- Postmortem examinations (offspring):
- Gross pathology and histopathology was examined
- Statistics:
- Not specified
- Reproductive indices:
- Not specified
- Offspring viability indices:
- Not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- No effect on survival of treated male and female rats were observed.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 11.5 mg/kg/day for male and 13.5 mg/kg/day for female, Decreased in body weight was observed in treated male and female rats as compared to control.
When treated wtih 30 mg/kg bw, slight Decreased in body weight was observed. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 11.5 mg/kg/day for male and 13.5 mg/kg/day for female, Decreased in food consumption was observed in treated male and female rats
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 11.5 mg/kg/day for male and 13.5 mg/kg/day for female, Decreased in water consumption was observed in treated male and female rats
- 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
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Changes in the epithelium of
nasal passages in adult females were observed at 13.5 mg/kg/day.
Systemic toxicity consisted of (1) duct hypertrophy of Bowman's gland with loss of alveolar cells,
(2) degeneration, disorganization, and/or
atrophy of the olfactory epithelium, and
(3) dilation of the Bowman's gland ducts. Changes in Bowman's glands were accompanied in all affected animals by degeneration, disorganization, and/or atrophy of the olfactory epithelium.
No effect were observed in male rats. - Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effect on Reproductive performance was observed in treated rats as compared to control.
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- mortality
- gross pathology
- reproductive performance
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decrease in F1 mean pup weight on Day 22 were observed as compared to control.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 11.5 mg/kg/day for male and 13.5 mg/kg/day female, marginal decreased in food consumption was observed in treated male and female rats
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- No effect on Reproductive performance was observed in treated F1 pups as compared to control.
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 11.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No effect on reproduction
- Remarks on result:
- other: No effect observed
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 13.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No effect on reproduction
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Decrease in mean body weight gain for F2 litters was observed.
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 11.5 mg/kg/day for male, decreases 8-9% in testes and epididymis weight in male pups in the F1a and F2a litters.
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 3.2 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: No effect observed
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 3.9 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- NOAEL was considered to be 11.5 mg/kg/day for male and 13.5 mg/kg/day female for P and F1 generation when Alpk: Apf SD male and female rats were treated with Metam-sodium orally by gavage for 65 days and more days.
- Executive summary:
In a Reproduction Toxicity Test, Alpk: Apf SD male and female rats were treated with Metam-sodiumin the concentration of 0,11.5 mg/kg/day for male and13.5 mg/kg/day female orally in drinking water for 65 days and more days.No effect on survival of treated male and female rats were observed.Decreased in body weight was observed at11.5 mg/kg/day for male and13.5 mg/kg/day female rats as compared to control.Slight Decreased in body weight was observed at 3.2 mg/kg bw in male and 3.9 mg/kg bw mg/kg bw in female. Decreased in food consumption and water consumption was observed at11.5 mg/kg/day for male and13.5 mg/kg/day female rats.Red spot on pituitary gland, Twisted snout was observed at11.5 mg/kg/day for male and13.5 mg/kg/day female. However relation to treatment was doubtful.Changes in the epithelium of nasal passages in adult females were observed at13.5 mg/kg/day. Systemic toxicity consisted of (1) duct hypertrophy of Bowman's gland with loss of alveolar cells,(2) degeneration, disorganization, and/oratrophy of the olfactory epithelium, and (3) dilation of the Bowman's gland ducts. Changes in Bowman's glands were accompanied in all affected animals by degeneration, disorganization, and/or atrophy of the olfactory epithelium.No effect were observed in male rats. Similarly, Decrease in F1 mean pup weight on Day 22 and marginal decreased in food consumption were observed at 11.5 mg/kg/day for male and13.5 mg/kg/day female as compared to control.Decrease in mean body weight gain for F2 litters was observed.Decreases 8-9% in testes and epididymis weight in male pups in the F1a and F2a litters at11.5 mg/kg/day in male rats were observed. In addition,No effect onReproductive performancewas observed in treated P and F1 rats as compared to control.Therefore, NOAEL was considered to be 11.5mg/kg/day for male and 13.5 mg/kg/day female for P and F1 generation when Alpk: Apf SD male and female rats were treated with Metam-sodium orally by gavage for in drinking water for 65 days and more days.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 13.5 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimish 4 and from European Commission
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity:
In different studies, Metam-sodium has been investigated for reproductive toxicity to a greater or lesser extent. Study based on in vivo experiments, i.e. most commonly in rats for Metam-sodium and summarized below
In a experimental study given by European Commission (European Commission, European Chemicals Bureau, 2000), Carlocket al(Handbook of Pesticide Toxicology, Chapter 87, Volume 2.2001.) and US EPA (United states environment protection agency, 1994), Alpk: Apf SD male and female rats were treated with Metam-sodiumin the concentration of 0, 11.5 mg/kg/day for male and 13.5 mg/kg/day female orally in drinking water for 65 days and more days. No effect on survival of treated male and female rats was observed. Decreased in body weight was observed at11.5 mg/kg/day for male and13.5 mg/kg/day female rats as compared to control. Slight Decreased in body weight was observed at 3.2 mg/kg bw in male and 3.9 mg/kg bw mg/kg bw in female. Decreased in food consumption and water consumption was observed at11.5 mg/kg/day for male and13.5 mg/kg/day female rats.Red spot on pituitary gland, Twisted snout was observed at11.5 mg/kg/day for male and13.5 mg/kg/day female. However relation to treatment was doubtful. Changes in the epithelium of nasal passages in adult females were observed at13.5 mg/kg/day. Systemic toxicity consisted of (1) duct hypertrophy of Bowman's gland with loss of alveolar cells,(2) degeneration, disorganization, and/oratrophy of the olfactory epithelium, and (3) dilation of the Bowman's gland ducts. Changes in Bowman's glands were accompanied in all affected animals by degeneration, disorganization, and/or atrophy of the olfactory epithelium. No effect were observed in male rats. Similarly, Decrease in F1 mean pup weight on Day 22 and marginal decreased in food consumption were observed at 11.5 mg/kg/day for male and13.5 mg/kg/day female as compared to control. Decrease in mean body weight gain for F2 litters was observed. Decreases 8-9% in testes and epididymis weight in male pups in the F1a and F2a litters at11.5 mg/kg/day in male rats were observed. In addition, No effect on Reproductive performance was observed in treated P and F1 rats as compared to control. Therefore, NOAEL was considered to be 11.5mg/kg/day for male and 13.5 mg/kg/day female for P and F1 generation when Alpk: Apf SD male and female rats were treated with Metam-sodium orally by gavage for in drinking water for 65 days and more days.
In another experimental study given by Carlocket al(Handbook of Pesticide Toxicology, Chapter 87, Volume 2.2001.), Wistar male and female rats were treated with Metam-sodium in the concentration of 0, 10, 40, or 120 mg/kg/day orally by gavage on Days 6-15 of gestation. Significantly decreased in body weight gain was observed in treated female rats at 40 and 120 mg/kg as compared to control. Cesarean section observations revealed that there was a statistically significant increase in the percentage of postimplantation loss and a significant decrease in the percentage of live fetuses per dam at 10 and 120 mg/kg. But not at the 40 mg/kg dose level. It is possible that the effects observed at the 10 mg/kg dose level were statistical anomalies, but this remains unconfirmed in the absence of a review of the individual data, which were not available. Since there were no statistically significant changes in Cesarean section observations in the 40 mg/kg group, it is likely that the statistically significant changes in percentage of live fetuses per dam and the percentage of postimplantation loss in the 10 mg/kg group are not treatment-related. In addition, significant decrease in fetal weight was observed at 120 mg/kg as compared to control. Meningocele (hernial protrusion of the meniges through a bony defect) in two fetuses from one litter at 120 mg/kg. Since this is a rare finding that was not present in historical controls, this anomaly was considered to be treatment-related. Increased incidence of variations and a delay in the development of fetuses were observed at 40 and 120 mg/kg. Therefore, NOAEL was considered to be 10 mg/kg/day for P and F1 generation when Wistar male and female rats were treated with Metam-sodium orally by gavage on Days 6-15 of gestation.
Further supported by experimental study given by Carlocket al(Handbook of Pesticide Toxicology, Chapter 87, Volume 2.2001.) and US EPA (United states environment protection agency, 1994), 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. 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.
Thus, based on the above studies on Metam-sodium, it can be concluded that Metam-sodium is toxic to reproduction till dose of 13.5 mg/kg bw. Thus, comparing this effect with the criteria of CLP regulation, Metam-sodium can be classified under “category II” for reproductive toxicity.
Thought, the test substance Metam-sodium is classified under category II, Metam-sodium is extensive and rapidly metabolize 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. Hence, Metam-sodium is show Low bio-accumulation potential. The ADI proposed by the RMS in the DAR was 0.001 (EFSA Scientific Report (2008) 203, 1-97) and Metam-sodium is use as a pesticide, plant fumigant to control weeds, nematodes, fungi, bacteria and insects (United states environment protaction agecny, 1994). Hence, Metam-sodium is considered to be of no safety concern.
Effects on developmental toxicity
Description of key information
NOAEL was considered to be 10 mg/kg/day for P and F1 generation when Wistar male and female rats were treated with Metam-sodium orally by gavage on Days 6-15 of gestation.
Thus, based on the above studies on Metam-sodium, it can be concluded that Metam-sodium is toxic to development till dose of 10 mg/kg bw. Thus, comparing this effect with the criteria of CLP regulation, Metam-sodium can be classified under “category II” for developmental toxicity.
Thought, the test substance Metam-sodium (CAS no 137-42-8) is classified under category II, Metam-sodium is extensive and rapidly metabolize 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. Hence, Metam-sodium is show Low bio-accumulation potential. The ADI proposed by the RMS in the DAR was 0.001 (EFSA Scientific Report (2008) 203, 1-97) and Metam-sodium is use as a pesticide, plant fumigant to control weeds, nematodes, fungi, bacteria and insects (United states environment protaction agecny, 1994). Hence, Metam-sodium is considered to be of no safety concern.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from Scondray source
- 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
- 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 - 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
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: An aqueous solution of metam sodium (42.2%) was administered at 0, 10, 40, or 120 mg/kg by gavage to pregnant Wistar rats
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 10 days
- Frequency of treatment:
- Daily
- Duration of test:
- Days 6-15 of gestation
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 10 mg/kg bw/day
- Dose / conc.:
- 40 mg/kg bw/day
- Dose / conc.:
- 120 mg/kg bw/day
- No. of animals per sex per dose:
- not specified
- Control animals:
- not specified
- Details on study design:
- not specified
- Maternal examinations:
- Body weight, Gross pathology and histopathology was examined.
- Ovaries and uterine content:
- Not specified
- Fetal examinations:
- Live fetuses, Gross pathology and histopathology was examined.
- Statistics:
- Not specified
- Indices:
- Not specified
- Historical control data:
- Not specified
- Clinical signs:
- not specified
- 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 40 and 120 mg/kg, significantly decreased in body weight gain was observed in treated female rats as compared to control.
- Food consumption and compound intake (if feeding study):
- not specified
- 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:
- no effects observed
- Description (incidence and severity):
- Reproductive performance:
When treated wtih 10 and 120 mg/kg, Cesarean section observations revealed that there was a statistically significant increase in the percentage of postimplantation loss and a significant decrease in the percentage of live fetuses per dam. But not at the 40 mg/kg dose level.
It is possible that the effects observed at the 10 mg/kg dose level were statistical anomalies, but this remains unconfirmed in the absence of a review of the individual data, which were not available.
Since there were no statistically significant changes in Cesarean section observations in the 40 mg/kg group, it is likely that the statistically significant changes in percentage of live fetuses per dam and the percentage of postimplantation loss in the 10 mg/kg group are not treatment-related. - Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 10 and 120 mg/kg, Cesarean section observations revealed that there was a statistically significant increase in the percentage of postimplantation loss and a significant decrease in the percentage of live fetuses per dam. But not at the 40 mg/kg dose level.
It is possible that the effects observed at the 10 mg/kg dose level were statistical anomalies, but this remains unconfirmed in the absence of a review of the individual data, which were not available. - Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- Since there were no statistically significant changes in Cesarean section observations in the 40 mg/kg group, it is likely that the statistically significant changes in percentage of live fetuses per dam and the percentage of postimplantation loss in
the 10 mg/kg group are not treatment-related. - 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
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- dead fetuses
- pre and post implantation loss
- Remarks on result:
- other: No effect observed
- Abnormalities:
- not specified
- Description (incidence and severity):
- not specified
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated wtih 120 mg/kg, Significant 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 with 120 mg/kg bw, meningocele (hernial protrusion of the meniges through a bony defect ) in two fetuses from one litter.
Since this is a rare finding that was not present in historical controls, this anomaly was considered to be treatment-related. - Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased incidence of variations and a delay in the development of fetuses at 40 and 120 mg/kg
- Visceral malformations:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 10 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
- Abnormalities:
- not specified
- Description (incidence and severity):
- not specified
- 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
- Conclusions:
- NOAEL was considered to be 10 mg/kg/day for P and F1 generation when Wistar male and female rats were treated with Metam-sodium orally by gavage on Days 6-15 of gestation.
- Executive summary:
In aTeratology study, Wistar male andfemale rats were treated withMetam-sodiumin the concentration of0, 10, 40, or 120mg/kg/day orally by gavage on Days 6-15 of gestation.Significantly decreased in body weight gain was observed in treated female rats at 40 and 120 mg/kg as compared to control.Cesarean section observations revealed that there was a statistically significant increase in the percentage of postimplantation loss and a significant decrease in the percentage of live fetuses per dam at10 and 120 mg/kg. But not at the 40 mg/kg dose level.It is possible that the effects observed at the 10 mg/kg dose level were statisticalanomalies, but this remains unconfirmed in the absence of a review of the individual data, which were not available.Since there were no statistically significant changes in Cesarean section observations in the 40 mg/kg group, it is likely that the statistically significant changes in percentage of live fetuses per dam and the percentage of postimplantation loss inthe 10 mg/kg group are not treatment-related. In addition, developmental effect such as Significant decrease in fetal weight were observed at120 mg/kgas compared to control.Meningocele (hernial protrusion of the meniges through a bony defect ) in two fetuses from one litter at 120 mg/kg.Since this is a rare finding that was not present in historical controls, this anomaly was considered to be treatment-related. Increased incidence of variations and a delay in the development of fetuses were observed at 40 and 120 mg/kg.Therefore, NOAEL was considered to be 10mg/kg/day for P and F1 generation whenWistar maleand female rats were treated withMetam-sodiumorally by gavage on Days 6-15 of gestation.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 10 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimish 4 and from Handbook of Pesticide Toxicology
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Developmental toxicity:
In different studies, Metam-sodium has been investigated for developmental toxicity to a greater or lesser extent. Study based on in vivo experiments, i.e. most commonly in rats for Metam-sodium and summarized below
In a experimental study given by Carlocket al(Handbook of Pesticide Toxicology, Chapter 87, Volume 2.2001.) and US EPA (United states environment protection agency, 1994), Wistar male and female rats were treated with Metam-sodium in the concentration of 0, 10, 40, or 120 mg/kg/day orally by gavage on Days 6-15 of gestation. Significantly decreased in body weight gain was observed in treated female rats at 40 and 120 mg/kg as compared to control. Cesarean section observations revealed that there was a statistically significant increase in the percentage of postimplantation loss and a significant decrease in the percentage of live fetuses per dam at 10 and 120 mg/kg. But not at the 40 mg/kg dose level. It is possible that the effects observed at the 10 mg/kg dose level were statistical anomalies, but this remains unconfirmed in the absence of a review of the individual data, which were not available. Since there were no statistically significant changes in Cesarean section observations in the 40 mg/kg group, it is likely that the statistically significant changes in percentage of live fetuses per dam and the percentage of postimplantation loss in the 10 mg/kg group are not treatment-related. In addition, significant decrease in fetal weight was observed at 120 mg/kg as compared to control. Meningocele (hernial protrusion of the meniges through a bony defect) in two fetuses from one litter at 120 mg/kg. Since this is a rare finding that was not present in historical controls, this anomaly was considered to be treatment-related. Increased incidence of variations and a delay in the development of fetuses were observed at 40 and 120 mg/kg. Therefore,
In another experimental study given by Carlocket al(Handbook of Pesticide Toxicology, Chapter 87, Volume 2.2001.) and US EPA (United states environment protection agency, 1994), 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.
Thus, based on the above studies on Metam-sodium, it can be concluded that Metam-sodium is toxic to development till dose of 10 mg/kg bw. Thus, comparing this effect with the criteria of CLP regulation, Metam-sodium can be classified under “category II” for developmental toxicity.
Thought, the test substance Metam-sodium (CAS no 137-42-8) is classified under category II, Metam-sodium is extensive and rapidly metabolize 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. Hence, Metam-sodium is show Low bio-accumulation potential. The ADI proposed by the RMS in the DAR was 0.001 (EFSA Scientific Report (2008) 203, 1-97) and Metam-sodium is use as a pesticide, plant fumigant to control weeds, nematodes, fungi, bacteria and insects (United states environment protaction agecny, 1994). Hence, Metam-sodium is considered to be of no safety concern.
Justification for classification or non-classification
Based on the above studies on Metam-sodium, it can be concluded that Metam-sodium is toxic to reproduction and development . Thus, comparing this effect with the criteria of CLP regulation, Metam-sodium can be classified under “category II” for developmental toxicity.
Thought, the test substance Metam-sodium (CAS no 137-42-8) is classified under category II, Metam-sodium is extensive and rapidly metabolize 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. Hence, Metam-sodium is show Low bio-accumulation potential. The ADI proposed by the RMS in the DAR was 0.001 (EFSA Scientific Report (2008) 203, 1-97) and Metam-sodium is use as a pesticide, plant fumigant to control weeds, nematodes, fungi, bacteria and insects (United states environment protaction agecny, 1994). Hence, Metam-sodium is considered to be of no safety concern.
Additional information
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