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: 219-006-1 | CAS number: 2312-35-8
- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 10th July 1989 to 11th August 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Propargite
- EC Number:
- 219-006-1
- EC Name:
- Propargite
- Cas Number:
- 2312-35-8
- Molecular formula:
- C19H26O4S
- IUPAC Name:
- propargite
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton Research Products, Denver, Pennsylvania, USA
- Age at study initiation: approximately 5-6 months
- Weight at study initiation: 3049-4528 g on gestation day 0
- Housing: individually in suspended stainless steel cages
- Diet: Certified Rabbit Chow® #5322 ad libitum
- Water: tap water ad libitum
- Acclimation period: 25-67 days
ENVIRONMENTAL CONDITIONS
- Temperature: 67-76 ºF (mean 71 ± 2.3 ºF)
- Humidity: 54-70 % (mean 62 ± 4.4 %)
- Photoperiod: 12 hrs dark / 12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
- The appropriate amount of test material was weighed into a beaker and the appropriate amount of corn oil added. The test material was stored at room temperature with fresh material prepared weekly. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Prior to test material administration, the 10 day stability of the test material stored at room temperature was established.
To ensure correct concentrations of the test material, analyses of the prepared dosing suspension was conducted prior to dosing on days 7 and 12. - Details on mating procedure:
- - Impregnation procedure: artificial insemination
- Duration of treatment / exposure:
- Days 7 to 19 of gestation
- Frequency of treatment:
- Daily
- Duration of test:
- Up to gestation day 29.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 mg/kg bw/day (nominal)
- Dose / conc.:
- 4 mg/kg bw/day (nominal)
- Dose / conc.:
- 6 mg/kg bw/day (nominal)
- Dose / conc.:
- 8 mg/kg bw/day (nominal)
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Twenty-five
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked: mortality and overt changes in appearance and behaviour.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily on days 7 to 29 of gestation.
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 7, 13, 20, 24 and 29 of gestation.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29. The abdominal and thoracic cavities and organs of the females were examined for grossly evident morphological changes and the carcasses discarded.
- Females not surviving to scheduled sacrifice were necropsied in an attempt to determine the cause of death.
OTHER:
- Any female showing signs of abortion or premature delivery was sacrificed on the day such evidence was seen and the aborted tissue examined and preserved. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: location of viable and non-viable foetuses - Fetal examinations:
- - External examinations: Yes [all per litter]
- Soft tissue examinations: Yes [all per litter]
- Skeletal examinations: Yes [all per litter]
- Head examinations: No - Statistics:
- Sex ratios of offspring compared using chi-squared test and/or Fisher's exact probability test. Proportion of resorbed/dead foetuses and post-implantation losses compared using Mann-Whitney test. Mean maternal body weight, corpora lutea, total implantations, number of live foetuses and pups compared with one-way analysis of variance using Bartlett's test for homogeneity of variance and the appropriate t-test to determine significance of differences.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Antemortem signs observed prior to abortion included hair loss, aborted material, anogenital staining, decreased defecation and emaciation
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- There were no treatment-related effects on survival. One animal in each of the 6 and 8 mg/kg bw/d groups died although the cause of death was not established.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- There was a significant reduction in body weight and in body weight gain of the 8 and 10 mg/kg animals but only during gestation days 7-20 (see Tables 1 and 2).
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- effects observed, treatment-related
- Description (incidence and severity):
- Abortions occurred in three, one and four females in the 4, 8 and 10 mg/kg bw/d groups, respectively. The abortions at 4 and 8 mg/kg bw/d were not considered to be treatment-related due to a lack of dose-response (no abortions at 6 mg/kg bw/d). The abortions at 10 mg/kg bw/d, however, were deemed to be treatment-related by virtue of the other signs of toxicity observed at this dose level.
- Pre- and post-implantation loss:
- not specified
- Description (incidence and severity):
- Following caesarean section, pre- and post-implantation losses and total implantations in treated animals were all comparable to the control group.
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- Following caesarean section, foetal viability in treated animals was comparable to the control group.
- 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:
- no effects observed
- Description (incidence and severity):
- Following caesarean section, corpora lutea in treated animals were comparable to the control group.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- maternal toxicity
- Effect level:
- 4 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Following caesarean section, foetal body weight in treated animals was comparable to the control group.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Following caesarean section, foetal body weight in treated animals was comparable to the control group. - Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- Following caesarean section, foetal viability in treated animals was comparable to the control group.
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- not specified
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Fused sternebrae was observed in kits from females treated at dose levels of 8 and 10 mg/kg bw/d (in 2/125 and 9/116 foetuses, respectively; 8 % of foetuses, 56 % of litters at 10 mg/kg/day). Fused skull bones were also noted in kits from these dose groups but there was no dose-response (2.4 % of foetuses, 17 % of litters at 8 mg/kg/day). There were no other treatment related malformations or developmental variations.
- Visceral malformations:
- not specified
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- developmental toxicity
- Effect level:
- 6 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1: Summary of body weight values (g)
0 mg/kg/day | 2 mg/kg/day | 4 mg/kg/day | 6 mg/kg/day | 8 mg/kg/day | 10 mg/kg/day | |||||||
Day of study | Mean | S.D. | Mean | S.D. | Mean | S.D. | Mean | S.D. | Mean | S.D. | Mean | S.D. |
0 | 3471 | 329.0 | 3570 | 360.7 | 3632 | 352.4 | 3664 | 358.2 | 3574 | 414.0 | 3530 | 329.0 |
7 | 3674 | 350.9 | 3784 | 398.1 | 3824 | 373.6 | 3811 | 376.3 | 3752 | 435.0 | 3733 | 347.5 |
13 | 3760 | 353.1 | 3872 | 374.4 | 3910 | 344.3 | 3824 | 343.3 | 3792 | 399.7 | 3679 | 248.8 |
20 | 3787 | 276.7 | 3950 | 361.3 | 3943 | 331.0 | 3849 | 365.6 | 3760 | 401.4 | 3648 | 272.3 |
24 | 3885 | 274.0 | 4001 | 419.6 | 4006 | 378.5 | 3904 | 371.4 | 3918 | 423.0 | 3781 | 227.2 |
29 | 3958 | 250.2 | 4110 | 358.3 | 4093 | 337.4 | 3985 | 334.8 | 4014 | 406.0 | 3907 | 261.3 |
Table 2: Summary of body weight gain values (g)
0 mg/kg/day | 2 mg/kg/day | 4 mg/kg/day | 6 mg/kg/day | 8 mg/kg/day | 10 mg/kg/day | |||||||
Day of study | Mean | S.D. | Mean | S.D. | Mean | S.D. | Mean | S.D. | Mean | S.D. | Mean | S.D. |
0-7 | 203 | 107.6 | 214 | 84.8 | 193 | 91.0 | 147 | 60.5 | 177 | 73.0 | 203 | 73.5 |
7-13 | 87 | 100.3 | 88 | 69.7 | 86 | 98.8 | 13 | 116.6 | 41 | 119.4 | -55 | 171.8 |
13-20 | 27 | 147.1 | 78 | 89.9 | 33 | 201.8 | 25 | 203.0 | -32 | 198.2 | -4 | 209.2 |
7-20 | 114 | 188.3 | 165 | 133.2 | 119 | 253.4 | 38 | 290.7 | 9 | 267.5 | -20 | 308.4 |
20-24 | 98 | 77.6 | 52 | 92.7 | 55 | 158.6 | 54 | 101.3 | 139 | 118.4 | 101 | 89.3 |
24-29 | 73 | 254.9 | 108 | 144.6 | 49 | 129.7 | 46 | 150.7 | 97 | 94.2 | 126 | 129.8 |
0-29 | 487 | 254.9 | 540 | 135.0 | 493 | 205.8 | 318 | 369.9 | 447 | 201.6 | 464 | 188.9 |
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the test, dose levels of 8 and 10 mg/kg bw/day led to maternal toxicity as evidenced by abortions at the 10 mg/kg level and significantly reduced body weight/body weight gain at both dose levels. The only potential developmental toxicity was manifested by fused sternebrae in a small percentage of kits from the 8 and 10 mg/kg bw/d females (i.e. from groups treated with a maternally toxic dose). However, this is a spontaneously occurring variation that is commonly seen in kits delivered by control animals (as supported by a large historical control database). Moreover, there were no other signs of developmental toxicity as evidenced by an absence of adverse effects on foetal viability, foetal body weight, pre- and post implantation losses, total implantations and corpora lutea. Detailed analysis of the litters containing kits with fused sternebrae indicate that only two litters contained >1 kit with the condition (3 and 2 foetuses in each, respectively), the other litters each containing just one kit exhibiting fused sternebrae, an incidence which would not be considered treatment-related. Taken with the absence of any other indications of developmental toxicity in this study, this very slight increase in incidence of a normally spontaneously occurring variation in just two litters is not considered to indicate a teratogenic potential for the test material. In addition, this developmental variation was not observed at dose levels below the maternally toxic dose of 8 mg/kg bw/d. Based on these results, the NOEL for maternal toxicity was determined to be 6 mg/kg bw/d; this value also covers the increased incidence of fused sternebrae seen in the 8 mg/kg bw/d animals.
- Executive summary:
New Zealand White rabbits were dosed with 0, 2, 4, 6, 8 and 10 mg/kg/day test material by oral gavage as a single daily dose on days 7 to 19 of gestation. Caesarean examinations were performed on all surviving females on gestation day 29 followed by teratologic examinations.
8 and 10 mg/kg/day does exhibited evidence of maternal toxicity with respect to abortions at the 10 mg/kg/day level and body weight inhibition/loss during the treatment period at both levels. There were malformed (fused) sternebrae in 2 and 9 kits respectively in the 8 and 10 mg/kg/day groups. This was the only evidence of developmental toxicity.
The NOEL was determined to be 6 mg/kg/day for both maternal and developmental toxicity.
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.
