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EC number: 939-538-4 | CAS number: 1471313-87-7
- 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:
- 2015-2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
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:
- Sodium 2-[methyloleoylamino]ethane-1-sulphonate
- EC Number:
- 205-285-7
- EC Name:
- Sodium 2-[methyloleoylamino]ethane-1-sulphonate
- Cas Number:
- 137-20-2
- Molecular formula:
- C21H41NO4S.Na
- IUPAC Name:
- sodium 2-[methyl(oleoyl)amino]ethanesulfonate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- The animal room was air-conditioned with adequate (above 10) air changes per hour The experimental room was continuously monitored for tem¬pera¬ture and relative humidity. The ranges for room tem¬pera¬ture and relative humidity were 20.5°C to 22.3°C and 51 to 65%, respectively. The animals were provided with a light cycle of 12 hours light and 12 hours dark.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Dosing per gavage commenced on day 5 of gestation and continued until day 19 of gestation. Dose volume was 10 mL per kg body weight.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability and homogeneity analysis. Dose formulation anaylsis.
- Details on mating procedure:
- Animals were paired as one male and one female in the evening hours and following morning each female was examined for vaginal smear or the presence of a copulation plug in the vagina. The presence of sperm in the vaginal smear was taken as positive evidence of mating (Day 0 of gestation).The maximum mating period observed was of eight days. During the mating phase, animals were housed on one male: one female basis. After successful mating, the females were returned to their original cage and housed individually during gestation.
- Duration of treatment / exposure:
- Day 5 of gestation until day 19 of gestation
- Frequency of treatment:
- Once daily
- Duration of test:
- The dosing commenced on day 5 of gestation and continued until day 19 of gestation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 24 female animals per dose group
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- Clinical signs were recorded at same time(s) each day taking into consideration the peak period of anticipated effects after dosing. The condition of the animals was recorded including mortality, moribundity, pertinent behavioral changes, and all signs of overt toxicity. Body weights were examined during the acclimatization period once weekly, on first day of pairing and weekly thereafter as well as on gestation days 0, 3, 5, 8, 11, 14 17 and 20.
- Ovaries and uterine content:
- At termination, the uteri were removed and the pregnancy status of the animals was ascertained. Gravid uteri including the cervix were weighed. The uteri of females were examined for the presence and number of implantation sites and the number of corpora lutea in the ovaries were determined for pregnant animals. The uterine content was examined for number of resorption, live and/or dead foetuses. The degree of resorption was described in order to estimate the relative time of death of the conceptus. Uteri that appear non-gravid were further examined by 5% ammonium sulphide staining to reveal any early resorption or post implantation loss.
- Fetal examinations:
- Each foetus was subjected to external examination, which included all visible structures, surfaces and orifices (including the oral cavity). One-half of the fetuses (alternating foetuses within the litter) independent of sex were processed for skeletal alterations (odd number) and remaining half (even number) of each litter were examined for visceral (soft tissue) alterations. On completion of external examination the foetuses selected for skeletal evaluation were eviscerated and placed in 70% isopropyl alcohol.
- Statistics:
- Statistical analysis was performed using statplus program. All the data was checked for Normality with Shapiro-Wilk W test and for Homogeneity with Bartlett Chi-Square test. Each group of animals was subjected to Analysis of Variance (ANOVA). Values were given as mean ± standard deviation (SD).
- Indices:
- Pre-implantation loss, post-implantation loss, sex ratio, variation incidence
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- In high dose (1000 mg/kg) group animals, burrowing followed by dullness and dyspnoea was observed shortly after dosing which subsided to normal after 3 hours post dosing from first day to last day of dosing. Only dullness was observed in some of the animals in intermediate dose (300 mg/kg) group following each gavage treatment which subsides to normal after 3 hours post dosing from first day to last day of dosing.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality was observed in any of the treated animal through out the scheduled treatment period.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No significant difference in the body weight and body weight gain (%) was observed in pregnant female animals of low (100 mg/kg), intermediate (300 mg/kg) and high dose (1000 mg/kg) groups. A statistically significant decrease in body weight was observed in high dose (1000 mg/kg) group when compared with low dose (100 mg/kg) group only on 20th day of gestation. However, this change was within the normal range with respect to age and sex of the strain of animals used. Hence, the changes in body weight and body weight gain were considered as biological variation without any toxicological relevance.
Detailed data see the tables in section "Any other information on results inc. tables" - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Feed consumption of pregnant female animals at low (100 mg/kg), intermediate (300 mg/kg) and high dose (1000 mg/kg) groups was not significantly different throughout the treatment period. A statistically significant decrease in feed consumption was observed in high dose (1000 mg/kg) group when compared with control (0 mg/kg), low (100 mg/kg) and intermediate dose (300 mg/kg) groups only on day 11th of gestation, and in control (0 mg/kg) group animals only on day 14th of gestation. These changes were within the normal range with respect to age and sex of the strain of animals used. Hence, these changes in feed consumption were considered as biological variation and thus not of toxicological relevance.
Detailed data see the tables in section "Any other information on results inc. tables" - 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):
- no effects observed
- Description (incidence and severity):
- Daily observations revealed no indications of general and functional pertinent behavioral changes.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No abnormality was observed in any of the female animals from control, low, intermediate and high dose groups. Bursal cyst was observed in right ovary of one female animal of low dose group as an incidental finding.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- No abortion noted througout the study period.
Data see tables in section "Any other information on results inc. tables" - Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- No pre- and/or post-implantation losses observed.
Data see tables in section "Any other information on results inc. tables" - Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- No litter losses by resorption observed.
Data see tables in section "Any other information on results inc. tables" - Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- No late resorptions observed.
Data see tables in section "Any other information on results inc. tables" - Dead fetuses:
- no effects observed
- Description (incidence and severity):
- No dead fetuses observed.
Data see tables in section "Any other information on results inc. tables" - Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- No changes on pregnancy duration observed.
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): No effects on pregnancy duration observed. - Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- All the female animals of control, low, intermediate and high dose groups showed positive evidence of mating. At necropsy, three females each of control, high and low dose groups and four females of intermediate dose group were found non pregnant. As all dose groups are comparably involved and no dose response occurred, this finding is not of toxicological relevance.
Detailed data see tables in section "Any other information on results inc. tables" - Other effects:
- no effects observed
- Description (incidence and severity):
- No significant difference was observed in the sex ratio of foetuses in low, intermediate and high dose groups or other reproductive indices.
Detailed data see tables in section "Any other information on results inc. tables" - Details on maternal toxic effects:
- No maternal effects of toxicological relevance observed throughout the study period.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: overall findings
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- No significant difference was observed in litter and foetus weight of low, intermediate and high dose groups.
Detailed data see tables in section "Any other information on results inc. tables"
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): No changes in fetal/pub body weights recorded.
Detailed data see tables in section "Any other information on results inc. tables" - Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- No significant differences were observed in early and late resorptions and in the number of live foetuses in all treatment groups.
Detailed data see tables in section "Any other information on results inc. tables" - Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- No significant difference was observed in the sex ratio of foetuses in low, intermediate and high dose groups.
Detailed data see tables in section "Any other information on results inc. tables" - Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- No significant difference was observed in litter size and the foetus weights in low, intermediate and high dose groups.
Detailed data see tables in section "Any other information on results inc. tables" - Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- External examination of foetuses revealed one small sized foetus in control, six in low dose, eight in intermediate dose and three in high dose group. However, statistical significant differences in respective body weights were not observed. As the external variations observed were randomly distributed across the groups and in the absence of any dose response relationship, these findings were considered as incidental and of no toxicological relevance.
Detailed data see tables in section "Any other information on results inc. tables" - Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Skeletal examination of foetuses revealed variations common in type and distribution for the strain of rats used. They were isolated and when expressed on a foetus/litter basis, no statistical significant differences between treatment groups and control animals were observed.
Skeletal examination at the dose levels of 100, 300 and 1000 mg/kg body weight thus did not indicate any test item-related effects.
Detailed data see tables in section "Any other information on results inc. tables" - Visceral malformations:
- no effects observed
- Description (incidence and severity):
- Variations observed during visceral examination of foetuses revealed variations common in type and incidence for the strain of rats used and were randomly distributed across all groups. A dose response relationship was not observed. Therefore these findings were considered as incidental findings and of no toxicological relevance.
Detailed data see tables in section "Any other information on results inc. tables" - Other effects:
- no effects observed
- Description (incidence and severity):
- No effects observed
- Details on embryotoxic / teratogenic effects:
- No effects observed
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
SUMMARY OF MORTALITY AND CLINICAL SIGNS
|
Group |
|||
1 |
2 |
3 |
4 |
|
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
Mortality |
Nil |
Nil |
Nil |
Nil |
Clinical signs |
Nil |
Nil |
Dullness |
Excessive burrowing, Dullness, Dyspnoea |
BODY WEIGHTS (G) – SUMMARY
FEMALE
Group |
Body weights (G) |
||||||||
Gestation Day |
|||||||||
|
0 |
3 |
5 |
8 |
11 |
14 |
17 |
20 |
|
Group 1 |
Mean |
227.25 |
232.75 |
238.29 |
246.21 |
256.15 |
266.79 |
281.79 |
306.38 |
SD |
10.01 |
9.73 |
9.59 |
9.57 |
11.22 |
12.63 |
18.22 |
25.60 |
|
Min |
210.2 |
214.4 |
218.2 |
224.8 |
232.2 |
245.2 |
251.4 |
263.1 |
|
Max |
244.2 |
250.2 |
253.8 |
260.4 |
270.2 |
290.2 |
323.4 |
352.1 |
|
N |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
|
Group 2 |
Mean |
228.79 |
235.81 |
242.44 |
250.46 |
259.14 |
270.67 |
286.48 |
310.64 |
SD |
10.46 |
10.67 |
11.56 |
11.34 |
12.33 |
15.51 |
15.11 |
17.30 |
|
Min |
212.4 |
218.3 |
224.1 |
232.1 |
238.2 |
243.4 |
260.2 |
274.3 |
|
Max |
244.6 |
251.4 |
267.1 |
273.8 |
282.2 |
294.1 |
310.5 |
338.2 |
|
N |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
|
Group 3 |
Mean |
225.28 |
231.71 |
238.18 |
246.19 |
256.07 |
266.52 |
279.71 |
298.19 |
SD |
11.39 |
10.20 |
10.37 |
11.19 |
11.86 |
13.16 |
14.74 |
19.09 |
|
Min |
209.1 |
218.1 |
224.0 |
230.4 |
238.2 |
247.1 |
259.1 |
269.2 |
|
Max |
245.3 |
249.2 |
256.8 |
270.4 |
281.3 |
292.1 |
310.1 |
332.1 |
|
N |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
|
Group 4 |
Mean |
224.95 |
231.49 |
238.42 |
246.10 |
255.90 |
266.32 |
278.81 |
293.96# |
SD |
10.61 |
10.47 |
10.32 |
9.68 |
10.54 |
11.75 |
13.28 |
14.84 |
|
Min |
210.6 |
220.1 |
226.3 |
233.2 |
240.1 |
249.2 |
259.2 |
268.1 |
|
Max |
246.8 |
252.8 |
255.2 |
260.2 |
271.1 |
286.2 |
304.1 |
321.4 |
|
N |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
#Significant at p ≤ 0.05 level with group 2
BODY WEIGHT GAIN (%) - SUMMARY
FEMALE
Group |
Body weights Gain (%) |
|||||||
Gestation Day |
||||||||
|
3 |
5 |
8 |
11 |
14 |
17 |
20 |
|
Group 1 |
Mean |
2.43 |
4.88 |
8.39 |
12.77 |
17.44 |
24.02 |
34.91 |
SD |
1.00 |
1.61 |
2.44 |
3.48 |
3.90 |
6.33 |
10.90 |
|
N |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
|
Group 2 |
Mean |
3.08 |
5.99 |
9.52 |
13.30 |
18.32 |
25.28 |
35.84 |
SD |
1.43 |
2.74 |
3.27 |
3.15 |
4.59 |
5.24 |
6.22 |
|
N |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
|
Group 3 |
Mean |
2.89 |
5.77 |
9.33 |
13.72 |
18.35 |
24.19 |
32.41 |
SD |
1.26 |
1.65 |
2.48 |
2.98 |
3.00 |
3.38 |
6.34 |
|
N |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
|
Group 4 |
Mean |
2.92 |
6.02 |
9.47 |
13.84 |
18.50 |
24.03 |
30.82 |
SD |
1.21 |
1.92 |
2.82 |
3.75 |
4.95 |
5.01 |
6.90 |
|
N |
21 |
21 |
21 |
21 |
21 |
21 |
21 |
FEED CONSUMPTION - SUMMARY
FEMALE
Group |
FEED CONSUMPTION (G/ANIMAL/DAY) |
|||||||
Gestation Day |
||||||||
|
0 - 3 |
3 - 5 |
5 - 8 |
8 - 11 |
11 - 14 |
14 - 17 |
17 - 20 |
|
Group 1 |
Mean |
17.40 |
19.26 |
20.26 |
21.99 |
23.99 |
24.16 |
23.85 |
SD |
1.48 |
3.45 |
1.87 |
1.72 |
2.15 |
2.79 |
2.88 |
|
Group 2 |
Mean |
18.06 |
19.15 |
19.62 |
21.91 |
23.09 |
23.43 |
22.91 |
SD |
2.03 |
3.96 |
2.76 |
2.48 |
1.48 |
1.82 |
2.88 |
|
Group 3 |
Mean |
17.59 |
19.97 |
19.47 |
22.04 |
23.23 |
23.55 |
23.38 |
SD |
2.53 |
5.38 |
3.28 |
2.58 |
2.40 |
2.26 |
3.17 |
|
Group 4 |
Mean |
17.04 |
17.93 |
18.71 |
19.10*#@ |
21.41* |
22.31 |
22.10 |
SD |
2.10 |
4.12 |
3.00 |
3.57 |
3.17 |
2.42 |
2.54 |
*Significant at p ≤ 0.05 level with group 1
#Significant at p ≤ 0.05 level with group 2
@Significant at p ≤ 0.05 level with group 3
PREGNANCY STATUS
GROUP |
G1 |
G2 |
G3 |
G4 |
DOSE (mg/kg bw) |
0 |
100 |
300 |
1000 |
FEMALE ANIMALS MATED |
24 |
24 |
24 |
24 |
PREGNANT FEMALE ANIMALS |
21 |
21 |
20 |
21 |
MACROSCOPIC FINDINGS- FEMALE
GROUP |
G1 |
G2 |
G3 |
G4 |
DOSE (mg/kg bw) |
0 |
100 |
300 |
1000 |
ANIMALS EXAMINED |
24 |
24 |
24 |
24 |
ANIMALS WITHOUT ABNORMALITY |
24 |
24 |
24 |
24 |
ANIMALS AFFECTED |
0 |
0 |
0 |
0 |
MATERNAL DATA - SUMMARY
Parameter |
Group |
G1 |
G2 |
G3 |
G4 |
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
|
No. of Dams |
21 |
21 |
20 |
21 |
|
Gravid Uterine Weight |
Mean |
43.9637 |
53.2278 |
45.9287 |
49.9408 |
SD |
16.0935 |
10.1451 |
14.7209 |
18.3332 |
|
No. of CL |
Mean |
11.96 |
12.92 |
12.92 |
12.58 |
SD |
2.73 |
1.77 |
2.34 |
2.80 |
|
No. of Implantation |
Mean |
8.13 |
9.92 |
8.38 |
9.13 |
SD |
4.24 |
4.15 |
4.83 |
4.76 |
|
No. of Foetuses |
Mean |
8.38 |
10.14 |
9.00 |
9.71 |
SD |
3.35 |
2.31 |
3.36 |
3.98 |
|
Early Resorption |
Mean |
0.79 |
0.88 |
0.88 |
0.54 |
SD |
0.88 |
1.15 |
1.08 |
0.88 |
|
Late Resorption |
Mean |
0.00 |
0.17 |
0.00 |
0.08 |
SD |
0.00 |
0.64 |
0.00 |
0.28 |
|
Pre implantation loss |
Mean |
3.83 |
3.00 |
4.54 |
3.46 |
SD |
4.31 |
3.41 |
4.32 |
3.71 |
|
% |
30.90 |
24.41 |
35.89 |
29.12 |
|
Post implantation loss |
Mean |
0.79 |
1.04 |
0.92 |
0.63 |
SD |
0.88 |
1.20 |
1.10 |
1.01 |
|
% |
12.59 |
14.49 |
12.01 |
9.14 |
|
Dam with resorption/s |
Number |
13 |
12 |
12 |
8 |
LITTER DATA - SUMMARY
Parameter |
Group |
G1 |
G2 |
G3 |
G4 |
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
|
No. of Dams |
24 |
24 |
24 |
24 |
|
No. of Litters |
21 |
21 |
20 |
21 |
|
Total No. of Foetuses |
176 |
213 |
180 |
204 |
|
Mean Litter Size |
8.38 |
10.14 |
9.00 |
9.71 |
|
No. of Live Foetuses |
Number |
176 |
213 |
179 |
204 |
Mean |
8.38 |
10.14 |
8.95 |
9.71 |
|
SD |
3.35 |
2.31 |
3.32 |
3.98 |
|
No. of Dead Foetuses |
Number |
0 |
0 |
1 |
0 |
Mean |
0 |
0 |
0.05 |
0 |
|
SD |
0.00 |
0.00 |
0.22 |
0.00 |
|
No. of Live Male Foetuses |
Number |
93 |
96 |
96 |
101 |
Mean |
4.43 |
4.57 |
4.80 |
4.81 |
|
SD |
2.58 |
1.89 |
2.12 |
2.52 |
|
No. of Live Female Foetuses |
Number |
83 |
117 |
83 |
103 |
Mean |
3.95 |
5.57 |
4.15 |
4.90 |
|
SD |
1.69 |
2.13 |
2.08 |
2.41 |
GROUP MEAN FOETUS WEIGHTS
Group |
Foetus weight/Litter (G) |
Foetus Weight (G) |
||
Male |
Female |
|||
Group 1 |
Mean |
3.3814 |
3.3354 |
3.4330 |
SD |
0.6200 |
0.6853 |
0.5369 |
|
N |
176 |
93 |
83 |
|
Group 2 |
Mean |
3.3860 |
3.4788 |
3.3099 |
SD |
0.5341 |
0.5384 |
0.5205 |
|
N |
213 |
96 |
117 |
|
Group 3 |
Mean |
3.3906 |
3.4430 |
3.3300 |
SD |
0.6227 |
0.6619 |
0.5720 |
|
N |
179 |
96 |
83 |
|
Group 4 |
Mean |
3.3245 |
3.3427 |
3.3066 |
SD |
0.7148 |
0.7441 |
0.6879 |
|
N |
204 |
101 |
103 |
GROUP MEAN SEX RATIO
Group |
Sex ratio (%) Male |
||
Group 1 |
Mean |
49.08 |
|
SD |
17.36 |
||
N |
176 |
||
Group 2 |
Mean |
45.26 |
|
SD |
16.60 |
||
N |
213 |
||
Group 3 |
Mean |
54.83 |
|
SD |
17.99 |
||
N |
180 |
||
Group 4 |
Mean |
50.21 |
|
SD |
17.08 |
||
N |
204 |
EXTERNAL FINDINGS
Group |
G1 |
G2 |
G3 |
G4 |
|
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
|
No. of Litter Examined |
21 |
21 |
20 |
21 |
|
No. of Foetuses Examined |
176 |
213 |
179 |
204 |
|
Variation Incidence – Number (%) |
|||||
No. of Foetus with Variations |
Total Variations |
1(0.57) |
6(2.82) |
8(4.47) |
3(1.47) |
a)Foetus small in size |
1(0.57) |
6(2.82) |
8(4.47) |
3(1.47) |
VISCERAL FINDINGS
Group |
G1 |
G2 |
G3 |
G4 |
|
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
|
No. of Litter Examined |
21 |
21 |
20 |
21 |
|
No. of Foetuses Examined |
84 |
103 |
84 |
97 |
|
Variation Incidence – Number (%) |
|||||
No. of Foetus with Variations |
Total Variations |
19(22.62) |
18(17.48) |
15(17.86) |
22(22.68) |
Spleen: Small in size |
8(9.52) |
7(6.80) |
5(5.95) |
7(7.22) |
|
Spleen: Pale |
5(5.95) |
4(3.88) |
4(4.76) |
8(8.25) |
|
Ureters: Convoluted |
6(7.14) |
7(6.80) |
6(7.14) |
7(7.22) |
SKELETAL FINDINGS
Group |
G1 |
G2 |
G3 |
G4 |
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
No. of Litter Examined |
21 |
21 |
20 |
21 |
No. of Foetuses Examined |
92 |
110 |
95 |
107 |
Variation Incidence – Number (%) |
||||
Hyoid |
||||
Not ossified |
1(1.09) |
0 |
0 |
0 |
Incompletely ossified |
1(1.09) |
0 |
0 |
4(3.74) |
Bipartite |
1(1.09) |
0 |
0 |
0 |
Absent |
1(1.09) |
0 |
0 |
0 |
Thoracic Vertebra |
||||
Dumbbell shaped |
21(22.83) |
26(23.64) |
18(18.95) |
34(31.78) |
Bipartite |
3(3.26) |
10(9.09) |
12(12.63) |
4(3.74) |
Lumbar Vertebra |
||||
Not ossified |
0 |
1(0.91) |
0 |
0 |
Dumbbell shaped |
0 |
1(0.91) |
0 |
0 |
Sacral Vertebra |
||||
Not ossified |
1(1.09) |
0 |
0 |
0 |
Incompletely ossified |
1(1.09) |
0 |
0 |
0 |
Caudal Vertebra |
||||
Not ossified |
6(6.52) |
4(3.64) |
0 |
5(4.67) |
Sternal centers (1) |
||||
Not ossified |
10(10.87) |
11(10.00) |
9(9.47) |
12(11.21) |
Incompletely ossified |
10(10.87) |
6(5.45) |
12(12.63) |
14(13.08) |
Sternal centers (2) |
||||
Not ossified |
5 (5.43) |
3(2.73) |
0 |
5(4.67) |
Incompletely ossified |
4(4.35) |
0 |
3(3.16) |
0 |
Misshapen/Irregular shaped |
0 |
2(1.82) |
1(1.05) |
0 |
Manubrium |
||||
Not ossified |
11 (11.96) |
5(4.55) |
1(1.05) |
7(6.54) |
Incompletely ossified |
3(3.26) |
0 |
4(4.21) |
0 |
SKELETAL FINDINGS (CONTD.)
Group |
G1 |
G2 |
G3 |
G4 |
|
Dose (mg/kg bw) |
0 |
100 |
300 |
1000 |
|
No. of Litter Examined |
21 |
21 |
20 |
21 |
|
No. of Foetuses Examined |
92 |
110 |
95 |
107 |
|
Variation Incidence – Number (%) |
|||||
Xyphiod |
|||||
Not ossified |
25 (27.17) |
27(24.55) |
41(43.16) |
41(38.32) |
|
Incompletely ossified |
13(14.13) |
17(15.45) |
8(8.42) |
4(3.74) |
|
Ribs - Left |
|||||
Waviness |
1 (1.09) |
0 |
0 |
9(8.41) |
|
Ribs - Right |
|||||
Waviness |
1 (1.09) |
0 |
0 |
10(9.35) |
|
Supernumerary |
0 |
0 |
0 |
1(0.93) |
|
Metacarpals - Left |
|||||
Not ossified |
0 |
2(1.82) |
0 |
1(0.93) |
|
Incompletely ossified |
1(1.09) |
0 |
0 |
0 |
|
Metacarpals - Right |
|||||
Not ossified |
0 |
2(1.82) |
0 |
1(0.93) |
|
Incompletely ossified |
1(1.09) |
0 |
1(1.05) |
0 |
|
Metatarsal - Left |
|||||
Not ossified |
1(1.09) |
4(3.64) |
0 |
1(0.93) |
|
Incompletely ossified |
3(3.26) |
0 |
0 |
0 |
|
Metatarsal - Right |
|||||
Not ossified |
1(1.09) |
4(3.64) |
0 |
2(1.87) |
|
Incompletely ossified |
3(3.26) |
0 |
0 |
0 |
|
Pubis - Left |
|||||
Incompletely ossified |
0 |
0 |
1(1.05) |
0 |
|
Pubis - Right |
|||||
Not ossified |
0 |
0 |
1(1.05) |
0 |
|
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) of test item HOSTAPON TPHC for maternal and embryofoetal toxicity in Wistar female rats via oral route was found to be the highest dose level employed i.e., 1000 mg/kg body weight/day
- Executive summary:
The test item,HOSTAPON TPHC(formulated in distilled water) was administered once daily by oral gavage to three treatment groups of twenty four pregnant female Wistar rats per group from day 5 to day 19 of gestation at dose levels of 100, 300 and 1000 mg/kg body weight/day. A control group of twenty four females were administered with vehicle (distilled water)alone.
Female animals treated at 1000mg/kg bw/day(high dose) showed burrowing followed by dullness and dyspnoea while female animals treated at 300 mg/kg bw/day (intermediate dose) showed only dullness shortly after each administration. These findings recovered to normal after 3 hours post dosing each day. These temporary effects can be regarded unspecific in nature due to minor local irritative effects caused by test item administration.
The evaluation of the reproductive organs of the dam, pre and post implantation loss, gravid uterine weight, litter size, viability of the foetus, litter weight and foetus weight, sex ratio of the foetus and the external, visceral and skeletal examination of the foetus revealed that HOSTAPON TPHC did not cause any maternal as well as embryo foetal toxicity up to the highest dose of 1000 mg/kg bw/day tested.
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