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EC number: 203-319-5 | CAS number: 105-65-7
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 2015- June 2015
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- A mixture of: O,O-di(1-methylethyl)trithio-bis-thioformate; O,O-di(1-methylethyl)tetrathio-bis-thioformate; O,O-di(1-methylethyl)pentathio-bis-thioformate
- EC Number:
- 403-030-6
- EC Name:
- A mixture of: O,O-di(1-methylethyl)trithio-bis-thioformate; O,O-di(1-methylethyl)tetrathio-bis-thioformate; O,O-di(1-methylethyl)pentathio-bis-thioformate
- Cas Number:
- 137398-54-0
- Molecular formula:
- C8H14O2S5, C8C14O2S6, C8H14O2S7
- IUPAC Name:
- Reaction mass of 0,0-di(1-methylethyl)trithio-bis-thioformate and 0,0-di(1-methylethyl)tetrathio-bis-thioformate and 0,0-di(1-methylethyl)pentathio-bis-thioformate
- Test material form:
- other: liquid
- Details on test material:
- Batch nu 1130018
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- Species and strain: Hannover Wistar rats (CRLHan)
Source: Charles River Laboratories, Research Models and
Services, Germany GmbH, Sandhofer Weg 7, D-
97633, from SPF colony
Justification of strain: The rat is regarded as a suitable rodent species for
reproduction studies and the test guideline states it is
the preferred rodent species. The Hannover Wistar rat
was selected due to experience with this strain in
teratology studies.
Animal health: Only healthy animals were used for the test, as certified
by the staff Veterinarian
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 18.2-22.8°C (target: 22 ± 3 °C)
Relative humidity: 34-66 % (target: 30-70%)
Ventilation: 15-20 air exchanges/hour
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- A constant volume of 4 mL/kg bw was administered to all dose groups, including the
controls. The individual volume of the treatment was based on the most recent
individual body weight of the animals.
The control or test item dose formulations were administered to mated, sperm positive
assumed pregnant female rats daily by oral gavage on a 7 days/week basis,
approximately at similar times, from Gestation Day (GD) 6 to GD19, according to the
following dosing scheme: - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability of the AS100 in the vehicle (peanut oil) was assessed in the conditions
employed on the study during the validation study (according to CiToxLAB study
code 14/497-901AN). According to the results, the test item is stable in vehicle in
concentration range of 5 mg/mL - 100 mg/mL for 14 days when stored refrigerated (2-
8ºC).
Analysis of test item formulations for concentration and homogeneity was performed
in the Test Site (Fumoprep Ltd.) using a quantitative IR spectroscopic method (Test
Site study code: FPBSTUDY-121-VAL1, Ref. 4). Duplicate samples (top, middle and
bottom samples) were taken from the test item formulations twice during the study
(during the first and last weeks of treatment). Similarly, one sample (duplicate) was
taken on each occasion from the Group 1 (control) solution for concentration
measurements. - Details on mating procedure:
- The oestrus cycle of female animals was examined shortly before start of pairing.
After acclimation, the females were paired according to their oestrus cycle with males
in the morning for approximately 2 hours (1 male: 1 females) until at least 24 sperm
positive females/group are attained. After the daily mating period, a vaginal smear
was prepared and stained with 1% aqueous methylene blue solution. The smear was
examined with a light microscope; the presence of a vaginal plug or sperm in the
vaginal smear was considered as evidence of copulation (GD0). Sperm positive
females were separated and caged individually - Duration of treatment / exposure:
- The dams (one control and 3-treated
groups) were treated daily by oral (gavage) administration, from gestation day GD6 up
to and including GD19 (sperm positive day = 0 day of pregnancy, GD0). Caesarean
sections, necropsy of dams and examination of uterine contents were performed on
GD20. The control animals were treated with vehicle only ( peanut oil) - Frequency of treatment:
- Daily treatment GD 6 to GD19
- Duration of test:
- Dosing scheme
Acclimatisation period 5 days- no dosing
Gestation days 5 to 19
Caesarean section and necroscopy Gestation day 20
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
23mg/kg/bw/day
Basis:
analytical conc.
- Remarks:
- Doses / Concentrations:
70mg/kg/day
Basis:
analytical conc.
- Remarks:
- Doses / Concentrations:
210 mg/kg/day
Basis:
analytical conc.
- No. of animals per sex per dose:
- 26-27 females per dose and control group
The number of confirmed pregnant, evaluated dams in the dose groups treated was 26
in the control group and 25 at treated groups. - Control animals:
- yes, concurrent vehicle
- Details on study design:
- accord to OECD 414
Examinations
- Maternal examinations:
- Maternal Data:
- Number of animals at test start, no. of animals surviving, no. of pregnant animals,
no. of animals with total intrauterine mortality
- Clinical signs (by gestation day)
- Mortality (by gestation day), if any
- Body weight and body weight gain: mean ± S.D.
- Corrected body weight on GD20 (body weight-gravid uterine weight) and
corrected body weight gain: mean ± S.D.
- Net body weight change (Body weight on GD20 minus body weight on GD6
minus gravid uterine weight): mean ± S.D.
- Food consumption: mean ± S.D.
- Gross pathology findings
- Gravid uterine weight
- Absolute and relative to body weight liver and spleen weights - Ovaries and uterine content:
- Caesarean Section and Necropsy Data:
- Number of corpora lutea: mean ± S.D.
- Number of implantations: mean ± S.D.
- Number and percent of live foetuses: mean ± S.D.
- Number and percent of intrauterine mortality: mean ± S.D.
Classified according to time of death: Pre-implantation loss, Post-implantation
mortality, Early and late embryonic, as well as foetal death
- Pre-implantation loss: %, group mean
UNumber of corpora lutea-Number of implantationsU x100
Number of corpora lutea
- Post-implantation loss: %, group mean
UNumber of implantations-Number of live foetusesU x100
Number of implantations - Fetal examinations:
- Sex distribution: %, group mean
UNumber of male (female) foetusesU x100
Number of foetuses
- Foetal body weight (accuracy 0.01 g): mean ± S.D.
- External abnormalities/litter: %, group mean
UNumber of foetuses with abnormalityU x100
Number of foetuses
- Visceral abnormalities/litter: %, group mean
UNumber of foetuses with abnormalityU x100
Number of foetuses
- Skeletal abnormalities/litter: %, group mean
UNumber of foetuses with abnormalityU x100
Number of foetuses - Statistics:
- Appropriate statistical method (Bartlett,
ANOVA and Duncan, Kruskal-Wallis and Mann-Whitney U tests, Chi2) using the
litter as the unit for data analysis. The homogeneity of variance between groups was
checked by Bartlett`s homogeneity of variance test. Where no significant
heterogeneity was detected a one-way analysis of variance (ANOVA) was made. If
the obtained result was significant Duncan’s Multiple Range test was used to assess
the significance of inter-group differences. Significant results with inter-group
comparisons were further compared using Kruskal-Wallis, and Mann-Whitney Utests. - Indices:
- Pre-implantation loss: %, group mean
UNumber of corpora lutea-Number of implantationsU x100
Number of corpora lutea
- Post-implantation loss: %, group mean
Number of implantations-Number of live foetuses/ Number of implantations x 100 - Historical control data:
- Historical control data was used to provide clear indications where toxicologically significant effects had occurred
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased body weigth gains and reducd food/water intake reduced.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased body weight gains.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced food consumption.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced water intake.
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatement related efects in the liver and spleen.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Clinical signs: Upon immediate administration of the test material to all treated groups was noted as a dose response effect. Clinical signs included piloerection, clonic convulsion, rooting in bedding and increased salivation.
Body Weight: At 23mg/kg/bw the dams had comparable body weights to control group. There was a marked initial body weight loss noted in mid and high dose groups with partial recovery over the timecourse. The corrected body weight ( adjusted for gravid uterine weight) for both mid and high dose was lower than the control attaining statistical signifcant result.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 23 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 70 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity - toxicologically significant test item realted to body weight and food consumption was observed at mid and high dose groups.
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
none
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 210 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: There was no treatment related effects seen at external, visceral or skeletal foetal examination
- Dose descriptor:
- NOAEL
- Effect level:
- 210 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: embryotoxicity - There was no treatment related effects seen at external, visceral or skeletal foetal examination
- Dose descriptor:
- NOAEL
- Effect level:
- 210 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity - There was no treatment related effects seen at external, visceral or skeletal foetal examination
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
- Lowest effective dose / conc.:
- 210 mg/kg bw/day (actual dose received)
- Treatment related:
- not specified
Any other information on results incl. tables
Mortality : There was no unscheduled mortality in the study.
Clinical signs: Upon immediate administration of the test material to all treated groups was noted as a dose response effect. Clinical signs included piloerection, clonic convulsion, rooting in bedding and increased salivation.
Body Weight: At 23mg/kg/bw the dams had comparable body weights to control group. There was a marked initial body weight loss noted in mid and high dose groups with partial recovery over the timecourse. The corrected body weight ( adjusted for gravid uterine weight) for both mid and high dose was lower than the control attaining statistical signifcant result.
The weight of liver and spleen were increased in mid and high dose groups but no statistically significant changes were seen in liver or spleen weight in low dose group.
Foetal Body weights: Mean foetal body weights were unaffected by maternal treament with test substance at any dose level. The incidence of body weight retarded foetuses was simliar in control and test item treated groups. The weight of foetuses at 23, 70 and 210 mg/kg bw/day did not differ significantly from the control mean, when evaluated by both litter mean and group mean.
Although the overall mean foetal body weights, and the mean weight of foetuses evaluated by litter mean, were statistically significantly higher at the low and mid dose levels (by 5.5 and 6.1%, respectively; all values were in the normal historical range and there was no clear dose response relationship. Therefore these statistical differences were considered not related to treatment.
Teratogenic/Embryotoxic effects: No foetal external abnormalities to the test item at all dose levels up to and including 210mg/kg/day.
No foetal visceral abnormalities are ascribed to the test item administration.
The mean number of corpora lutea and the mean number of implantation sites were comparable with the controls in all treated groups. The pre-implantation loss was at control level in all treated groups. The total intrauterine mortality was comparable with the control. The early and the late embryonic loss did not differ significantly from the control in the test item treated groups. There was no statistically significant difference in foetal death compared to the control.
Applicant's summary and conclusion
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