Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-308-5 | CAS number: 105-55-5
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Comparable to guideline study [OECD 414] A read-across between DMTU (dimethylthiourea) and DETU (diethylthiourea) is justified because theirs structures differ by a methyl fonction only. DETU has a molecular weight more higher than DMTU and therefore DETU is probably less toxic than DMTU.
Data source
Reference
- Reference Type:
- publication
- Title:
- Difference in the developmental toxicity of ethylenethiourea and three N,N-substituted thiourea derivatives in rats.
- Author:
- Saillenfait AM, Sabate JP, Langonne J and de Ceaurriz J.
- Year:
- 1 991
- Bibliographic source:
- Fundam. Appl. Toxicol. 17: 399-408
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1,3-dimethyl-2-thiourea
- EC Number:
- 208-588-2
- EC Name:
- 1,3-dimethyl-2-thiourea
- Cas Number:
- 534-13-4
- Molecular formula:
- C3H8N2S
- Reference substance name:
- N,N'-Dimethylthiourea
- IUPAC Name:
- N,N'-Dimethylthiourea
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: From IFFA CREDO Breeding Laboratories (St Germain sur l'arbresle, France)
- Age at study initiation: no data
- Weight at study initiation: males = 350 g ; females = 200-220 g
- Fasting period before study: no data
- Housing: Bred females were individually housed in clear polycrbonate cages with hardwood shavings as bedding.
- Diet (e.g. ad libitum): UAR Alimentation Villemoisson, ad libitum
- Water (e.g. ad libitum): filetred tap water, ad libitum
- Acclimation period: 1 or 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- °C
- Humidity (%): 55 +/- 5%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): a light cycle from 7AM to 7 PM
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Administered volume = 5 ml/kg bw
The actual volume administered was based on body weight taken on GD6. - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1M / 3 F
- Length of cohabitation: overnight
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- gestation days 6 to 20
- Frequency of treatment:
- daily, at approximately the same time each time
- Duration of test:
- 1 month
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 15, 25, 50, 100 and 200 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 20-23 animals/dose
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes, daily
DETAILED CLINICAL: no data
BODY WEIGHT : Yes, on day 0 and every 3 days from days 6 to 21 of gestation.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: uterus - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Live and dead fetuses - Fetal examinations:
- Fetal body weight & Fetal malformations
live fetuses were removed, weighed, sexed and examined.
- External examinations: Yes: all per litter (including those of the oral cavity)
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes:half per litter
- Head examinations: Yes: No data - Statistics:
- Whenever possible, the data were presented as means ± SD. Implantation sites, live fetuses, and various body weights were analyzed by the one-way analysis of variance, followed by Dunnett's test if differences were found. The frequency of nonsurviving implants, resorptions, and anomalies among litters was evaluated with the Dixon-Massey test after an arc-sine-square root transformation. Rates of pregnancy and fetal sex ratio were analyzed using Fisher's exact test. Where applicable, least-squares analysis was carried out. The reported level of statistical significance was p < 0.05.
- Indices:
- no data
- Historical control data:
- no data
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- No maternal deaths, morbidity, or treatment-related clinical signs were observed during this study. Significant reduction of maternal body weight gain was observed in tha last third of gestation at 15 mg/kg bw/d and throughout treatment at higher dose levels. The maternal weight gain during days 6 to 21 of gestation and the absolute weight gain were significantly reduced at all doses (p<0.01) (table 1). Incidences of pregnancy were comparable among groups (table 2).
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- < 15 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- No significant effect of DMTU was noted on the mean numbers of implantation sites, viable fetuses, and percentage of resorptions and on fetal sex ratio. fetal body weights were significantly reduced at all doses tested, showing a dose-depenent relationship. The 9% decrease at 15 mg/kg bw/d reached 34% at 200 mg/kg bw/d (Table 2). The decrease in maternal weight was considered severe aand the fetal effects caused by DMTU were probably secondary to the toxicity incurred by the mothers.
No animalies were seen upon external examination of the fetuses (table 3). Dilated ureter and extra lumbar ribs occurred significantly more often among litters of rats given 200 mg/kg bw/d (p<0.01 and p<0.05, respectively). No other visceral and skeletal variants were significantly affected at any tested dose. In the control group, one fetus exhibited a forelimb syndactiyly and onother a bilateral microphtalmia.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- < 15 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- Dose descriptor:
- NOAEL
- Effect level:
- > 200 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1 : change in weight during gestation in SD rats treated daily by gastric intubation with DMTU on days 6 to 20 of gestation and sacrified on day 21a
Compound |
Dose |
Body weight (g) on GD6 |
Body weight gain (g) |
Absolute weight gain (g)b |
|||||
GD 6-9 |
GD 9-12 |
GD 12/15 |
GD 15-18 |
GD 18-21 |
GD 6-21 |
||||
Distilled water (ml/kg/d) |
5 |
257+/-14 |
18+/-5 |
16+/-6 |
24+/-5 |
48+/-7 |
59+/-10 |
162+/-19 |
46+/-17 |
DMTU (mg/kg/d) |
15 |
255+/-16 |
15+/-4 |
15+/-5 |
19+/-6 |
40+/-9* |
46+/-11** |
135+/-24** |
33+/-10** |
25 |
255+/-14 |
12+/-6* |
16+/-5 |
17+/-6** |
38+/-9** |
41+/-10** |
126+/-24** |
28+/-13** |
|
50 |
256+/-11 |
6+/-5** |
19+/-6 |
15+/-5** |
35+/-11** |
34+/-9** |
109+/-21** |
19+/-10** |
|
100 |
253+/-15 |
3+/-10** |
11+/-7* |
14+/-7** |
25+/-8** |
35+/-9** |
88+/-20** |
3+/-10** |
|
200 |
257+/-16 |
-1+/-4** |
14+/-7 |
8+/-6** |
22+/-8** |
27+/-9** |
71+/-14** |
-2+/-11** |
|
Data are expressed as means +/- SD aIncludes all dams pregnant at sacrifice. GD = gestational day. b(day 21 bw) – (gravid uterus weight) – (day 6 bw) * and ** denote significant differences from the vehicle control value using Dunnett’s test, p<0.05 and p<0.01, respectively. |
Table 2 : Reproductive parameters in SD rats treated daily by gastric intubation with DMTU on days 6 to 20 of gestation and sacrified on day 21a
Compound |
Dose |
No. of deaths per number of treated females |
% of females pregnant |
Number of examined litters |
Mean implantation sites per litter |
Mean live fetuses per litter |
Mean % nonsurviving implants per litterb |
Mean % resorption sites per litter |
Distilled water (ml/kg/d) |
5 |
0/20 |
95.0 |
19 |
15.26+/-1.94 |
14.95+/-1.96 |
2.02+/-3.70 |
2.02+/-3.70 |
DMTU (mg/kg/d) |
15 |
0/21 |
85.7 |
18 |
14.39+/-3.47 |
14.06+/-3.45 |
2.24+/-4.08 |
2.24+/-4.08 |
25 |
0/21 |
95.2 |
20 |
14.50+/-3.32 |
14.15+/-3.59 |
3.63+/-6.44 |
3.63+/-6.44 |
|
50 |
0/21 |
90.5 |
19 |
13.79+/-3.85 |
13.26+/-3.75 |
3.49+/-5.55 |
3.49+/-5.55 |
|
100 |
0/23 |
95.6 |
22 |
14.81+/-3.17 |
14.04+/-2.90 |
4.73+/-6.14 |
4.73+/-6.14 |
|
200 |
0/23 |
87.0 |
20 |
14.40+/-2.85 |
13.70+/-2.87 |
4.68+/-7.19 |
4.27+/-7.20 |
|
Data are expressed as means +/- SD aIncludes all dams pregnant at sacrifice. GD = gestational day. bResorption plus dead fetuses * and ** denote significant differences from the vehicle control value using Dunnett’s test, p<0.05 and p<0.01, respectively. |
Compound |
Dose |
Fetal sex ratio M:F (%) |
Mean fetal body weight (g) per litter |
|
Males |
Females |
|||
Distilled water (ml/kg/d) |
5 |
0.86 |
6.00+/-0.30 |
5.68+/-0.29 |
DMTU (mg/kg/d) |
15 |
1.14 |
5.47+/-0.33** |
5.19+/-0.34** |
25 |
0.96 |
5.29+/-0.30** |
5.04+/-0.25** |
|
50 |
1.15 |
5.20+/-0.33** |
4.80+/-0.36** |
|
100 |
0.98 |
4.40+/-0.28** |
4.26+/-0.29** |
|
200 |
0.89 |
3.94+/-0.28** |
3.76+/-0.24** |
|
Data are expressed as means +/- SD * and ** denote significant differences from the vehicle control value using Dunnett’s test, p<0.05 and p<0.01, respectively. |
Table 3 : Incidence of anomalies in fetuses of SD rats teated daily by gastric intubation with DMTU on days 6 to 20 of gestation and sacrified on day 21
|
Distilled Water (ml/kg/d) |
DMTU (mg/kg/d) |
||||
|
5 |
15 |
25 |
50 |
100 |
200 |
|
Number of fetuses (litters) examined |
|||||
External examination |
284 (19) |
253 (18) |
283 (20) |
252 (19) |
309 (22) |
274 (20) |
Soft tissue examination |
142 (19) |
127 (18) |
142 (20) |
126 (19) |
154 (22) |
137 (20) |
Skeletal examination |
142 (19) |
126 (18) |
141 (20) |
126 (19) |
155 (22) |
137 (20) |
|
Number of fetuses (litters) affected |
|||||
Soft tissue anomalies |
|
|
|
|
|
|
Microphtalmiab |
1 (1) |
0 |
0 |
0 |
0 |
0 |
Hydroureter |
0 |
0 |
0 |
0 |
0 |
3 (2) |
Dilated renal pelvis |
1 (1) |
0 |
0 |
0 |
1 (1) |
5 (2) |
Dilated ureter |
0 |
0 |
0 |
0 |
1 (1) |
18 (11) ** |
Skeletal anomaliesInterparietal and/or occipital not ossified |
0 |
0 |
0 |
0 |
0 |
0 |
Vertebral centra dumbbell-shaped or absent |
0 |
2 (2) |
0 |
2 (2) |
3 (3) |
4 (3) |
Extra lumbar ribs |
9 (4) |
9 (6) |
8 (7) |
13 (6) |
14 (8) |
13 (13)* |
Fifth sternebrae Not ossified |
4 (4) |
0 |
1 (1) |
0 |
0 |
2 (2) |
Forelimb syndactilyly |
1 (1) |
0 |
0 |
0 |
0 |
0 |
bConsidered to be a malformation * and ** denote significant differences from the vehicle control value, p<0.05 and p<0.01, respectively. |
Applicant's summary and conclusion
- Conclusions:
- DMTU was not teratogenic in rat at 200 mg/kg bw/day, which was maternally toxic. But DMTU was fetotoxic at all doses tested in the presence of maternal toxicity.
- Executive summary:
A read-across between these two substances is justified for the reproduction endpoint.
Because DETU and DMTU are two thioureas having a high structural similarity: both structures differ by a carbon by chain.
Moreover DETU and DMTU have the same physicalchemical properties, and are harmful by oral route (acute toxicity).
Saillenfait,et al (1991), tested DMTU in SD rats at 0, 15, 25, 50, 100 or 200 mg/kg/day from GD 6-20.
The only maternal toxicity noted was decreased body weight gain at 15 mg/kg/day and above (NOAEL of maternal toxicity < 15 mg/kg bw/d). The LOAEL for developmental toxicity was 15 mg/kg/day based on decrease of fetal body weight gain at all doses. The decrease in maternal weight was considered severe and the fetal effects caused by DMTU were probably secondary to the toxicity incurred by the mothers. Dilated ureter and extra lumbar ribs were observed at 200 mg/kg bw/d (significant results).
No teratogenic effects related to administration of DMTU were observed at dose levels up to 200 mg/kg bw/d, a level which was toxic to the dams.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.