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EC number: 235-845-6 | CAS number: 13005-36-2
- 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:
- supporting study
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Documentation insufficient for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- The Embryotoxic Action of Some Food Aromatisers
- Author:
- Zaitsev AN & Magenova NB
- Year:
- 1 975
- Bibliographic source:
- Voprosy Pitaniya.3:64-68
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- In the present article the results are cited of investigation into the action of phenylacetic acid on the embryo when they had been administered daily and perorally to female rats throughout the course of their pregnancy.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Phenylacetic acid
- EC Number:
- 203-148-6
- EC Name:
- Phenylacetic acid
- Cas Number:
- 103-82-2
- IUPAC Name:
- phenylacetic acid
- Details on test material:
- No data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- No data
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Details on mating procedure:
- No data
- Duration of treatment / exposure:
- Administered daily and perorally to female rats throughout the course of their pregnancy.
- Frequency of treatment:
- Daily
- Duration of test:
- From the start of pregnancy to the first month of the post-natal period.
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
45 mg/kg bw
Basis:
no data
- Remarks:
- Doses / Concentrations:
5 mg/kg bw
Basis:
no data
- No. of animals per sex per dose:
- In Experimental and control groups there were 14-15 female rats
- Control animals:
- yes
- Details on study design:
- - Other: Studies were carried out of the possible embryotoxic action of several synthetic fragment substances that go into the composition of an essence which is set aside for the aromatising of foodstuffs. It was established that phenylacetic acid which has been introduced into pregnant rats in large doses (0.2 LD50) during the critical periods of embryogenesis (the periods of implantation and organogenesis), while giving rise to no obvioud anomalies in the development of the embryos, showed some embryotoxic action, the degree of expression expression of which varied in te presence of the various substances. Phenylacetic acid showed the most marked result. In light of this, experiments were conducted using very large doses, exceeding by 2 -3000 times the actual addition of aromatisers to human food. The findings gave no basis on which to conclude on either the danger or safety of the given synthetic substances in relation to their embryotoxicity, but they did point to the advisability of carrying out further investigations.
Examinations
- Maternal examinations:
- No data
- Ovaries and uterine content:
- No data
- Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: No data - Statistics:
- No data
- Indices:
- No data
- Historical control data:
- No data
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
Investigation in 20-day old embryos in all groups observed no anomaly in the structure of the body and internal organs in comparison to the control.The number of live embryos belonging to one female and their weights were close in the experimental and control animals. Essentially, there was no difference in the indices of embryonal mortality in the two groups. Table (1). The content of nucleic acids in the liver of embryos from rats which recieved phenylacetic acid in a quantity equivalent to 0.02 LD50, and also in embryos from control animals fluctuated between identical limits and averaged; ribonucleic acid - 55.06 mg % in the experimental groups and 52.71 mg % in the control; deaoxyribonucleic acid -28.88 mg % (experimental) and 29.98 mg % (control).
On studying the indices which characterise the production and development of progeny, there were no verifiable distinctions. The length of prognancy, the number of live young belonging to one female, and the average weight at birth in the experimental and control groups could not be distinguished. Instances of stillbirth were not recorded. The development of hairy coats and the opening of eyes took place at the same time in both groups. Their weights after a month were also close. (Table 2).
Examination of the skeletons of 15 embryos from each group (in each group the centres of ossification in 570 bones were measured) showed that the centres of ossifications of the lower jaw, humerus and pelvic girdle in embryos from rats that had recieved phenylacetic acid in a dose equal to 0.02 LD50, were smaller in size than in embryos from control animals. Where the female rat had recieved a dose of 0.02 LD50 of phenylacetic acid, the differences in the size of the centres of ossification between the two groups were not in evidence. (Table 3).
Both the results of earlier investigations and the present study bear witness to the fact that phenylacetic acid exerts a breaking effect on the process of ossification of the skeleton of the embryos and this action depends both on the dose and on the period of its administration to the pregnant rats. The largest expression of this was observed when a single large dose (0.2 LD50) of phenylacetic acid was introduced during the critical periods of pregnancy; and the least expression when frequent doses equal to 0.2 LD50 were administered to the organism, and were not expressed at all when frequent doses equal to 0.002 LD50 were given.
Work by Creave and Parke and other researchers, have shown that because of the increased levels in the tissues of the pregnant animal of progesterone and pregnanediol, the conjugation with glucuronic acid of foreign substances significantly decreases. Therefore, phenylacetic acid being introduced into the organism of the rat during pregnancy when conjugation with glucuronic acid is lower, is capable in certain dosages of having a negative effect on progeny.
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1 Indices of fertility and state of foetus
Experiment |
Aromatizer |
LD50 |
Overall foetal mortality (in parts of a unit) |
Difference |
Average number of young |
Average embryo weight |
Experiment I |
Phenylacetic acid |
0.02 |
0.17±0.08 |
>0.1 |
12 |
2.3 |
Control |
|
0.26±0.04 |
|
11 |
2.4 |
|
Experiment II |
Phenylacetic acid |
0.002 |
0.24±0.09 |
|
11 |
2.3 |
Control |
|
0.28±0.03 |
|
11 |
2.2 |
Table 2. Indices characterising production and development of rat progeny
Experiment |
Aromatizer |
LD50 |
Average length of pregnancy in days |
Average number of offspring per female |
Average weight of young at birth |
Average weight after one month |
Development of coat (in days) |
Opening of eyes ( in days) |
Experiment I |
Pl henylacetic acid |
0.02 |
22 |
12 |
6.9 |
69 |
7-9 |
17-18 |
Control |
|
23 |
11 |
6.8 |
70 |
7-9 |
17-19 |
|
Experiment II |
Phenylacetic acid |
0.002 |
22 |
10 |
6.2 |
82 |
9-10 |
16-17 |
Control |
|
22 |
8 |
6.7 |
86 |
9-10 |
16-17 |
Table 3. Size of centres of ossification in the skeletons of embryos subjected to the action of phenylacetic acid and control embryos.
Bone |
Experiment I |
Difference |
Experiment II |
||
Control |
Phenylacetic acid 0.02 LD50 |
Control |
Phenylacetic acid 0.002 LD50 |
||
Lower Jaw |
|
|
|
|
|
Left |
7144±46.22 |
6877±46.22 |
<0.001 |
6880±100 |
6917±26 |
Right |
7138±46.22 |
6917±46.22 |
<0.01 |
6904±92 |
6981±62 |
Parietal |
|
|
|
|
|
Left |
5160±30.82 |
5120±62.23 |
|
5120±107 |
5221±123 |
Right |
5160±46.22 |
5120±46.22 |
|
5133±108 |
5208±31 |
Clavicle |
|
|
|
|
|
Left |
2834±15.40 |
2736±27.73 |
<0.01 |
2752±43 |
2736±31 |
Right |
2829±21.60 |
2720±27.73 |
<0.01 |
2757±43 |
2749±49 |
Scapula |
|
|
|
|
|
Left |
2476±21.55 |
2386±21.57 |
<0.01 |
2346±22 |
2400±25 |
Right |
2480±6.39 |
2720±27.73 |
<0.001 |
2328±28 |
2405±25 |
Humerus |
|
|
|
|
|
Left |
2666±30..82 |
2533±27.73 |
<0.01 |
2560±40 |
2605±63 |
Right |
2672±30.82 |
2528±30.82 |
<0.01 |
2586±46 |
2631±46 |
Ulna |
|
|
|
|
|
Left |
2797±43.58 |
2589±30.74 |
<0.01 |
2600±59 |
2605±63 |
Right |
2810±43.99 |
2578±40.06 |
<0.01 |
2610±52 |
2658±46 |
Radius |
|
|
|
|
|
Left |
2101±33.90 |
1976±21.57 |
<0.01 |
1965±46 |
1985±37 |
Right |
2112±30.84 |
1974±27.73 |
<0.01 |
2002±40 |
1986±31 |
Table 3 Continued.
Bone |
Experiment I |
Difference |
Experiment II |
||
Control |
Phenylacetic acid 0.02 LD50 |
Control |
Phenylacetic acid 0.002 LD50 |
||
Metacarpals |
|
|
|
|
|
Left II |
205±15.4 |
176±12.32 |
|
162±9 |
166±12 |
III |
328±15.4 |
288±15.4 |
<0.05 |
262±12 |
274±12 |
IV |
253±12.33 |
213±9.24 |
<0.05 |
198±6 |
200±9 |
Metacarpals |
|
|
|
|
|
II |
208±15.4 |
181±15.40 |
|
165±12 |
164±12 |
III |
328±15.4 |
288±15.41 |
|
275±15 |
289±9 |
IV |
250±20.8 |
221±15.41 |
|
205±12 |
208±9 |
Ilium |
|
|
|
|
|
Left |
1734±27.72 |
1594±33.90 |
<0.01 |
1656±31 |
1640±18 |
Right |
1741±28.50 |
1608±33.90 |
<0.05 |
1648±31 |
1640±21 |
Ischium |
|
|
|
|
|
Left |
934±15.41 |
778±15.41 |
<0.05 |
744±22 |
748±25 |
Right |
829±9.24 |
744±18.49 |
<0.01 |
746±22 |
786±31 |
Pubic |
|
|
|
|
|
Left |
496±21.57 |
389±33.9 |
<0.02 |
434±28 |
455±18 |
Right |
520±30..82 |
397±33.9 |
<0.01 |
450±34 |
469±25 |
Femur |
|
|
|
|
|
Left |
1885±33.9 |
1778±46.23 |
|
1794±38 |
1792±50 |
Right |
1901±30.84 |
1792±46.23 |
|
1816±46 |
1808±46 |
Tibia |
|
|
|
|
|
Left |
2256±46.23 |
21.17±46.23 |
<0.05 |
2048±34 |
2112±49 |
Right |
2176±33.49 |
21.09±46.23 |
|
2050±40 |
2120±55 |
Fibula |
|
|
|
|
|
Left |
2106±43.23 |
19.68±46.23 |
|
1941±46 |
1973±43 |
Right |
2080±40.06 |
19.38±43.15 |
|
2050±40 |
2120±55 |
Metatarsals |
|
|
|
|
|
Left II |
210±15.41 |
189±15.41 |
|
162±17 |
125±13 |
III |
277±12.33 |
237±15.41 |
|
226±15 |
200±12 |
IV |
320±18.49 |
269±21.57 |
|
264±15 |
216±12 |
Right II |
208±15.41 |
186±15.41 |
|
160±12 |
128±12 |
III |
264±15.41 |
242±12.33 |
|
210±12 |
200±15 |
IV |
314±15.41 |
269±15.41 |
<0.05 |
248±15 |
226±15 |
Applicant's summary and conclusion
- Conclusions:
- Phenylacetic acid, administered orally to rats throughout pregnancy at a dosage of 45 mg/kg, did exhibit some embryotoxic action which was expressed by the slowing down of the process of ossification of separate centres in the skeletons of progeny. There were no other visible external or internal anomalies in development, having observed the progeny for the first month after birth, there did not appear to be any verifiable differences between the experimental and control animals. However, phenylacetic acid administered to rats in the same conditions but at a dose of 5 mg/kg, exhibited no embryotoxic action.
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