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EC number: 201-114-5 | CAS number: 78-40-0
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: Guideline study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Qualifier:
- according to guideline
- Guideline:
- other: EPA TSCA Test Guidelines (401 CFR Parts 796, 797, 798: 798.4900 Developmental Toxicity Study, September 27, 1985, and Revised Edition May 20, 1987)
- Qualifier:
- according to guideline
- Guideline:
- other: EC guidelines (Commision Directive 88/302/EEC, Official Journal of the European Communities L 133, May 30, 1988).
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Triethyl phosphate
- EC Number:
- 201-114-5
- EC Name:
- Triethyl phosphate
- Cas Number:
- 78-40-0
- Molecular formula:
- C6H15O4P
- IUPAC Name:
- triethyl phosphate
- Details on test material:
- purity: 99,83 %
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- The animals were mated by placing two females in a Type III cage with one male rat overnight. If sperm was found in a vaginal smear taken on the morning following mating, this day was regarded as day 0 of gestation.
- Duration of treatment / exposure:
- from day 6 to day 15 p.c.
- Frequency of treatment:
- daily
- Duration of test:
- The fetuses were delivered by cesarian section on the 20th day of gestation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 625 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 25/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The dose levels were selected according to a preceding rang-finding study in 4-5 rats with doses of 300, 500, and 625 mg/kg bw/d.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes, twice daily
DETAILED CLINICAL OBSERVATIONS: Yes, twice daily
BODY WEIGHT: Yes, on days 0, 6-15, and 20 pc
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20 - Ovaries and uterine content:
- according to Guideline
- Fetal examinations:
- External, visceral and skeletal examination of the fetuses
- Statistics:
- Fisher's exact significance test for fertility rate and gestation rate
F-test and t-test or Welch t-test for feed intakes, body weight gains, number of corpora lutea per dam, implantations per dam, live fetuses per dam etc.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The appearance and behavior of the dams was unaffected up to and including the dosage of 125 mg/kg.The dams of the 625 mg/kg group revealed clinical signs like bloddy mouth, staggering gait and ventral posture. The staggering gait and the ventral posture are considered to be a sign of the narcotic efficacy of TEP.
- Mortality:
- no mortality observed
- Description (incidence):
- one dam of the control group died on day 18 pc
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- body weight gains of the dams in the 625 mg/kg bw group statistically significant reduced between day 6-15 pc (15.1 versus 23.9 g in control) and day 0-20 corrected (24.5 versus 31.8 g); food consumption was lower in this dose group on day 6-11 pc.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment related findings were evident at necropsy up to and including the dose of 625 mg/kg bw.
Maternal developmental toxicity
- Description (incidence and severity):
- The number of corpora lutea, preimplantation losses and implantations were comparable in all experimental groups, with exception of the significantly lower preimplantation losses in the 25 mg/kg bw group.
- Description (incidence and severity):
- none
- Description (incidence and severity):
- the number of resorptions
- Description (incidence and severity):
- no changes
- Description (incidence and severity):
- No. of pregnants: 22, 20, 22, 20
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- none: fetal body weight. 3.48, 3.55, 3.59, 3.44 g in control, low, mid, high dose group
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- none: No. of fetuses per dam: 10.5, 11.6, 11.6, 10.6 in control, low, mid, high dose group
- Changes in sex ratio:
- no effects observed
- External malformations:
- no effects observed
- Description (incidence and severity):
- see Table
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- see Table
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- see Table
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
External, visceral and skeletal examination of the fetuses revealed no effects on intrauterine development
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 625 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no treatment related effects on development at any dose
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
External, skeletal and visceral malformations in viable fetuses:
| Malformation | Dose (mg/kg b.w./day) | |||
| 0 | 25 | 125 | 625 | |
| fetuses/ (Litters Affected) (n) | - | - | - | - |
| Microphtalmia | 1 | 1 | 1 | 2 (2) |
| Hydrocephalus internus | - | - | - | 1 |
| Pelvis dislocated | 1 | - | - | - |
| Malformation of vertebra | 4 (3) | - | 1 | 1 |
| Fusion of ribs | 1 | - | - | - |
| Thickened cervical rib | 1 | - | - | - |
| Malformation of forelimb bones | 1 | - | - | - |
| Exoccipitale dysplastic | 1 | - | - | - |
| Dislocation of atlanto-occipital joint (probably artifact +) | - | 1 | - | 1 |
| Fetuses per group (n) | 231 | 232 | 242 | 213 |
| malformed fetuses (n) | 7 | 2 | 2 | 5 |
| (%) | 3,0 | 0,9 | 0,8 | 2,4 |
| Litters per Group (n) | 22 | 20 | 22 | 20 |
| Litters with malformations (n) | 5 | 2 | 1 | 3 |
| (%) | 22,7 | 10,0 | 5,0 | 15,0 |
+ = nevertheless included in the calculation
some fetuses revealed more than one malformation, therefore the number of malformations does not necessarily reflect the number of fetuses affected.
Applicant's summary and conclusion
- Executive summary:
In a developmental toxicity study following OECD 414 groups of 25 inseminated female Wistar rats per dose group were treated daily by gavage with TEP formulated in demineralised water from days 6 to day 15 p.c. in doses of 0, 25, 125 or 625 mg/kg body weight, respectively. The fetuses were delivered by cesarian section on day 20 of gestation.
The dams of the 625 mg/kg group revealed clinical signs like bloddy mouth, staggering gait and ventral posture. The staggering gait and the ventral posture are considered to be a sign of the narcotic efficacy of TEP.
Body weight gain (day 6 -15 p.c.), feed intake (day 6 -11p.c.) and accordingly the feces excretion were reduced in the 625 mg/kg group.
The intrauterine development was not affected by the treatment including external, visceral and skeletal examination of the fetuses. A teratogenic potential was not evident.
The NOAEL were:
Maternal toxicity: 125 mg/kg bw./day
Developmental toxicity: 625 mg/kg bw./day.
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