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EC number: 204-524-2 | CAS number: 122-14-5
- 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:
- weight of evidence
- Study period:
- 16 December 1985 - 17 January 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Fenitrothion
- EC Number:
- 204-524-2
- EC Name:
- Fenitrothion
- Cas Number:
- 122-14-5
- Molecular formula:
- C9H12NO5PS
- IUPAC Name:
- O,O-dimethyl O-3-methyl-4-nitrophenyl phosphorothioate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 41208
Purity: 96.6%
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazelton, Denver
- Age at study initiation: 4 months
- Weight at study initiation: 2.7-3.2 kg
- Housing: Individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 28 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 15-64
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 16 December 1985 To: 17 January 1986
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- Groups of 16 inseminated female HRA(NZW)SPF rabbits each received fenitrothion dissolved in corn oil, at dose levels of 0, 3, 10 and 30 mg/kg bw/d by oral gavage, daily from Days 7 to 19 of gestation at a dosage volume of 1.0 mL/kg bw.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Reserve samples of the dosing solutions were analysed for stability and achieved concentration.
- Details on mating procedure:
- Ovulation was induced in each females by iv injection of 250 IU HCG; females were inseminated with the sperm of males from the same strain on two occasions. The day of inseminatiom was designated GD0.
- Duration of treatment / exposure:
- GD7-19 (13 consecutive days).
- Frequency of treatment:
- Daily
- Duration of test:
- Dams were terminated on GD 29
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle control
- Dose / conc.:
- 3 mg/kg bw/day
- Dose / conc.:
- 10 mg/kg bw/day
- Dose / conc.:
- 30 mg/kg bw/day
- No. of animals per sex per dose:
- 16 inseminated females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Doses were selcetd on the basis of range-finding studies in pregnant and non-pregnant rabbits. Animals were assigned to the treatment groups using a weight randomisation technique.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: GD 0, 7, 8, 9, 13, 16, 19, 20, 23, 26, 29
FOOD CONSUMPTION: Yes
- Time schedule for examinations: GD 0, 7, 8, 9, 13, 16, 19, 20, 23, 26, 29
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29 - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes / No / No data
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: Yes: all per litter - Statistics:
- Data were analysed and test groups compared to the controls using appropriate statistical techniques
- Indices:
- Not applicable
- Historical control data:
- Not required for this study
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Anorexia was frequently noted in all groups during the treatment and posttreatment periods. Treatment-related clinical signs in rabbits receiving 30 mg/kg bw/d included reduction in motor activity, salivation, dyspnoea, and tremors. These signs were not seen in any animals of the control, 3 and 10 mg/kg bw/d groups at the pre-treatment and post-treatment intervals, with only one incidence of reduced motor activity (10 mg/kg bw/d group) noted during treatment, in the decedent rabbit.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- A total of six pregnant females receiving 30 mg/kg/ bwd were found dead during the treatment period and three pregnant females aborted or delivered prematurely (GD 22-29). One female receiving 10 mg/kg bw/d was found dead on GD18, and one control female was found dead on GD 8. Both females were anorexic prior to death. The two deaths in the 3 mg/kg bw/d group were the result of dosing errors (verified at necropsy).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weight changes were significantly decreased for pregnant females receiving 30 mg/kg bw/d on GD7-13. These animals also displayed values slightly lower than the control for GD0-29 but this difference was not statistically significant.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Significantly decreased food consumption values were observed for pregnant females receiving 3 mg/kg bw/d on GD9-13 and were significantly increased for animals receiving 30 mg/kg bw/d on GD26-29 in addition to a significant negative trend on GD7-8. All other mean food consumption values were statistically similar for all groups.
- 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
- Description (incidence and severity):
- The findings were considered to be incidental and not related to treatment.
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Three pregnant females at 30 mg/kg bw/d aborted or delivered prematurely (GD 22-29).
- 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:
- effects observed, treatment-related
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- A total of six pregnant females receiving 30 mg/kg/ bwd were found dead during the treatment period and three pregnant females aborted or delivered prematurely (GD 22-29). One female receiving 10 mg/kg bw/d was found dead on GD18, and one control female was found dead on GD 8. Both females were anorexic prior to death. The two deaths in the 3 mg/kg bw/d group were the result of dosing errors (verified at necropsy). Anorexia was frequently noted in all groups during the treatment and posttreatment periods. Treatment-related clinical signs in rabbits receiving 30 mg/kg bw/d included reduction in motor activity, salivation, dyspnoea, and tremors. These signs were not seen in any animals of the control, 3 and 10 mg/kg bw/d groups at the pre-treatment and Mean body weight changes were significantly decreased for pregnant females receiving 30 mg/kg bw/d on GD7-13. These animals also displayed values slightly lower than the control for GD0-29 but this difference was not statistically significant.post-treatment intervals, with only one incidence of reduced motor activity (10 mg/kg bw/d group) noted during treatment, in the decedent rabbit. Significantly decreased food consumption values were observed for pregnant females receiving 3 mg/kg bw/d on GD9-13 and were significantly increased for animals receiving 30 mg/kg bw/d on GD26-29 in addition to a significant negative trend on GD7-8. All other mean food consumption values were statistically similar for all groups. Gross necropsy diod not reveal any effects of treatment.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- mortality
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- effects observed, treatment-related
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- The mean number of implantations was lower in the high dose group, resulting in a lower litter size. Other parameters were unaffected by treatment. There was no dose-related increase in the incidence of any particular malformation or in the incidence of any type (i.e. external, visceral, or skeletal) of malformation. Although the litter incidence of skeletal malformations was slightly higher than controls in the 3 and 10 mg/kg bw/d groups, no malformations were noted in the seven litters of the 30 mg/kg bw/d group available for evaluation. Overt evidence of maternal toxicity was seen in animals receiving 30 mg/kg/ bwd but was not accompanied by adverse effects on fetal growth or development
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 30 mg/kg bw/day
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- yes
- Relevant for humans:
- no
Any other information on results incl. tables
Summary of maternal findings
Dose level |
0 mg/kg bw/d |
3 mg/kg bw/d |
10 mg/kg bw/d |
30 mg/kg bw/d |
GD 7-19 (treatment period) |
||||
Number of animals observed |
16 |
16 |
16 |
16 |
Found dead |
1 |
0 |
1 |
6 |
Accidental death |
0 |
2 |
0 |
0 |
Reduction in motor activity |
0 |
0 |
1 |
14 |
Salivation |
0 |
0 |
0 |
14 |
Dyspnoea |
0 |
0 |
0 |
14 |
Tremors |
0 |
0 |
0 |
14 |
GD 20-29 (post-treatment period) |
||||
Number of animals observed |
15 |
14 |
15 |
10 |
Premature delivery/abortion |
0 |
0 |
0 |
3 |
Reduction in motor activity |
0 |
0 |
0 |
1 |
Food consumption (g) |
||||
GD 0-7 |
1124 |
1137 |
1161 |
1183 |
GD 7-8 |
126 |
102 |
108 |
91 |
GD 8-9 |
138 |
112 |
134 |
104 |
GD 9-13 |
548 |
441* |
531 |
465 |
GD 13-16 |
329 |
316 |
307 |
296 |
GD 16-19 |
364 |
221 |
307 |
294 |
GD 19-20 |
95 |
101 |
107 |
83 |
GD 20-23 |
385 |
372 |
372 |
403 |
GD 23-26 |
333 |
352 |
314 |
387 |
GD 26-29 |
278 |
396 |
307 |
457* |
Bodyweight change (g) |
||||
GD 0-7 |
169 |
149 |
166 |
148 |
GD 7-8 |
-31 |
-42 |
-47 |
-48 |
GD 7-9 |
-10 |
-38 |
-18 |
-68 |
GD 7-13 |
51 |
-2 |
29 |
-62* |
GD 7-16 |
45 |
33 |
61 |
-83 |
GD 7-19 |
92 |
-25 |
27 |
-73 |
GD 7-20 |
85 |
-9 |
35 |
-104 |
GD 7-23 |
168 |
63 |
87 |
4 |
GD 7-26 |
192 |
114 |
141 |
50 |
GD 7-29 |
228 |
203 |
192 |
141 |
*significantly different to controls (p<0.05)
Summary of litter parameters
Dose level |
0 mg/kg bw/d |
3 mg/kg bw/d |
10 mg/kg bw/d |
30 mg/kg bw/d |
Number of females inseminated |
16 |
16 |
16 |
16 |
Pregnancy rate (%) |
87.5 |
93.8 |
100.0 |
100.0 |
No. of pregnant females |
13 |
13 |
15 |
8 |
Number of litters with live foetuses |
13 |
13 |
13 |
7 |
Mean number of corpora lutea |
11.7 |
11.4 |
11.0 |
10.1 |
Mean number of implantations |
8.3 |
7.6 |
8.3 |
5.7 |
Mean implantation efficiency (%) |
72.5 |
67.9 |
76.8 |
61.5 |
Mean number of resorptions |
1.7 |
1.2 |
1.3 |
1.1 |
Mean incidence of resorptions (%) |
18.4 |
15.0 |
22.4 |
21.1 |
Mean incidence of foetal viability (%) |
81.6 |
84.0 |
77.6 |
78.9 |
Mean number of live foetuses per litter |
6.6 |
6.4 |
6.9 |
4.6 |
Mean number of dead foetuses per litter |
0.0 |
0.1 |
0.0 |
0.0 |
Mean percent of males per litter |
60.0 |
40.0 |
48.4 |
66.9 |
Mean fetal weight (g) |
|
|
|
|
Male |
44.6 |
43.6 |
41.1 |
48.0 |
Female |
42.9 |
42.6 |
40.5 |
45.0 |
Summary of foetal findings
Dose level |
0 mg/kg bw/d |
3 mg/kg bw/d |
10 mg/kg bw/d |
30 mg/kg bw/d |
Number of foetuses (fetal incidence %) |
||||
Total number of foetuses examined |
86 |
83 |
104 |
32 |
External malformations |
1 (1.2) |
0 (0.0) |
3 (2.9) |
0 (0.0) |
External variations |
0 (0.0) |
0 (0.0) |
1 (1.0) |
0 (0.0) |
Visceral malformations |
0 (0.0) |
2 (2.4) |
0 (0.0) |
0 (0.0) |
Visceral variations |
4 (4.7) |
1 (1.2) |
5 (4.8) |
1 (3.1) |
Skeletal malformations |
2 (2.3) |
6 (7.2) |
4 (3.8) |
0 (0.0) |
Skeletal variations |
67 (78) |
64 (77) |
79 (76) |
25 (78) |
Number of litter (litter incidence %) |
||||
Total number of litters examined |
13 |
13 |
13 |
7 |
External malformations |
1 (7.7) |
0 (0.0) |
2 (15) |
0 (0.0) |
External variations |
0 (0.0) |
0 (0.0) |
1 (7.7) |
0 (0.0) |
Visceral malformations |
0 (0.0) |
2 (15) |
0 (0.0) |
0 (0.0) |
Visceral variations |
3 (23) |
1 (7.7) |
4 (31) |
1 (14) |
Skeletal malformations |
1 (7.7) |
2 (15) |
3 (23) |
0 (0.0) |
Skeletal variations |
13 (100) |
13 (100) |
13 (100) |
7 (100) |
Applicant's summary and conclusion
- Conclusions:
- Maternal and developmental NOAELs of 10 mg/kg bw/d can be determined for this study, based on maternal toxicity (mortality, clinical signs, bodyweight effects) and reduced litter size at the highest dose level.
- Executive summary:
In a developmental toxicity study, groups of 16 inseminated female HRA(NZW)SPF rabbits each received fenitrothion dissolved in corn oil, at dose levels of 0, 3, 10 and 30 mg/kg bw/d by oral gavage, daily from Days 7 to 19 of gestation at the dosage volume of 1.0 mL/kg bw. Clinical observations, body weights and food consumption were recorded for all females. On day 29 of gestation, all surviving pregnant females were sacrificed and a cesarean section performed. All live fetuses were evaluated for external findings, visceral findings (Staples' technique) and for skeletal findings following staining with Alizarin Red S. A total of six pregnant females receiving 30 mg/kg/ bwd were found dead during the treatment period and three pregnant females aborted or delivered prematurely (GD 22-29). One female receiving 10 mg/kg bw/d was found dead on GD18, and one control female was found dead on GD 8. Both females were anorexic prior to death. The two deaths in the 3 mg/kg bw/d group were the result of dosing errors (verified at necropsy). Anorexia was frequently noted in all groups during the treatment and posttreatment periods. Treatment-related clinical signs in rabbits receiving 30 mg/kg bw/d included reduction in motor activity, salivation, dyspnoea, and tremors. These signs were not seen in any animals of the control, 3 and 10 mg/kg bw/d groups at the pre-treatment and Mean body weight changes were significantly decreased for pregnant females receiving 30 mg/kg bw/d on GD7-13. These animals also displayed values slightly lower than the control for GD0-29 but this difference was not statistically significant.post-treatment intervals, with only one incidence of reduced motor activity (10 mg/kg bw/d group) noted during treatment, in the decedent rabbit. Significantly decreased food consumption values were observed for pregnant females receiving 3 mg/kg bw/d on GD9-13 and were significantly increased for animals receiving 30 mg/kg bw/d on GD26-29 in addition to a significant negative trend on GD7-8. All other mean food consumption values were statistically similar for all groups. Gross necropsy did not reveal any effects of treatment. The mean number of implantations was lower in the high dose group, resulting in a lower litter size. Other parameters were unaffected by treatment. There was no dose-related increase in the incidence of any particular malformation or in the incidence of any type (i.e. external, visceral, or skeletal) of malformation. Although the litter incidence of skeletal malformations was slightly higher than controls in the 3 and 10 mg/kg bw/d groups, no malformations were noted in the seven litters of the 30 mg/kg bw/d group available for evaluation. Overt evidence of maternal toxicity was seen in animals receiving 30 mg/kg/ bwd but was not accompanied by adverse effects on foetal growth or development. Maternal and developmental NOAELs of 10 mg/kg bw/d can be determined for this study, based on maternal toxicity (mortality, clinical signs, bodyweight effects) and reduced litter size at the highest dose level.
The highest dose level in this study was sufficient to cause maternal toxicity (including mortality) and was associated with a slight reduction in implantations and litter size. Findings are considered to be secondary to maternal effects.
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