Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 200-021-7 | CAS number: 50-24-8
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on developmental toxicity
Description of key information
Prednisolone appeared to induce cleft palate if used in the first trimester of pregnancy.
Additional information
The induction of abnormal palatal development by three glucocorticoids, prednisolone, triamcinolone acetonide and hydrocortisone was evaluated in rat fetuses. Pregnant rats were injected subcutaneously with prednisolone (12.5 -100 mg/kg/day) on days 14 and 15 of gestation. These females were humanely killed on day 20 of gestation and viable fetuses were inspected for palatal abnormalities. The frequencies of cleft palate were significantly higher in the group treated with 100 mg/kg/day prednisolone (10.6%) than the control frequency of 0%. Prednisolone shows an ED50 value of 70 mg/kg/day. Other developmental abnormalities including omphalocele and general edema, late resorption, and growth retardation were induced by prednisolone. (Watanabe, C. et al.1995)
In a study to Sprague-Dawley rats, groups of 27 and 29 pregnant female were given daily oral doses of 0, 3, 30, or 100 mg/kg bw/day from day 6 to 15 of gestation. Two further groups were administered with 200 mg/kg bw/day causing severe maternal toxicity. Doses of 30 mg/kg bw/day and above caused increased embryolethality and reduced foetal weight. At 30 mg/kg bw/day two (out of 344) fetuses were malformed; one with cleft palate and one with omphalocele. (Fritz, H. et al. 1990)
Pregnant Holtzman rats were injected subcutaneously with anti-inflammatory drugs from day 12 to15 of gestation. Cleft palate was not induced by prednisolone even by daily doses ranging from 8-75 mg. Similar experiments were performed on A/J mice. The possible significance of these experiments in relation to testing potential teratogens and to the mechanism of palate closure is discussed in the article.
This work underscore as the teratogenic action of a glucocorticoid is unpredictable between species. If this hypotesis is true it becames pointless to rest for teratogenicity of drugs in rodents, since the only purpose of such testing is to extrapolate to man. Such extrapolation is very provisional at best. Thus, a single genetic background is not sufficient to evaluate the teratogenic potential of a drug. (Walker, B.E. 1971)
Intramuscular injections of prednisolone to New Zeland White rabbits were carried out to investigate the induction of cleft palate. Prednisolone was administered at doses of 1, 1.5, 2, 3, 4, or 8 mg /day from day 13 to 16 of gestation. No cases of cleft palate were observed in the foetusesfrom dams receiving 1 mg/day. Frequency of cleft palate increased with increasing dose levels from 1.5 to 4 mg/day until the point of complete litter resorption was reached at 8 mg/day. (Walker, B.E. 1967)
Prednisolone given 0.5 mg daily to A-JAX mice during mid-pregnancy produced a 77% incidence of cleft palate in the offspring. (Pinsky, L. et al.1965)
The effect of prenatal administration in hamster of different doses of prednisolone on the fetus and its palatal development was studied. Pregnant females were treated by a singular intramuscular injection of 7 to 20 mg/kg bw on day 11 of gestation. A dose-related incidence of frequency of cleft palate and the degree fetal growth retardation was observed. At 10 mg/kg bw was observed 93% incidence of cleft palate to reach 100% at 15 mg/kg bw. Moreover, at 20 mg/kg bw the rate of resorption was significantly higher than that of the control. (Shah, R.M. et al. 1976)
Swiss ICR:Ha albino pregnant mice were treated with prednisolone to evaluate the incidence of induced dead embryos, resorptions and cleft palate. The females received a single 50, 100, 200, or 330 mg/kg dose by intramuscular injection. From 100 to 330 mg/kg an increase of embryos resorptions was observed. The results demonstrate that prednisolone did not produce any increases in cleft palate even when administered at level up to 200 mg/kg. Prednisolone did produce consistent significant increase in cleft palate when administered in day 10 at 330 mg/kg. (Zawoiski, E.J. 1980)
Pregnant CD-1 mice were treated by direct application to eye of the solution or the suspension of prednisolone five times per day on gestation days 10 through 13. Ocularly applied prednisolone is adsorbed sistemically in sufficient quantity to produce teratogenic effects in mouse fetuses. The teratogenic effects observed were cleft palate and sex organ anormalities. When compared to control, the incidences of cleft palates were significantly higher (p<0.05) in all dosages reaching the plateau, already at the medium dose concentration, of 47% cleft palate. Ophthalmically applied prednisolone did produce incidences of cleft palate comparable to those produced by prednisolone administered intramuscularly or subcutaneously. (Ballard, P.D. et al. 1977)
Weigh of evidence studies:
CASE REPORT STUDY - The cause of risk to the fetus appears to be that of failure of placental function, manifesting itself either as a chronic process with a small fetus or as acute hypoxia in labour. This effect is apparently a direct result of prednisolone, since fetal mortality in the control group was low. The effect is not a disturbance of fetal adrenal function, since none of the babies gave clinical evidence of adrenocortical insufficiency. Experimental work suggests that placentation is damaged by glucocorticoids; Blackburn et al. (1965) found that the administration of prednisolone to pregnant rats inhibited placental growth, caused morphological changes resembling premature ageing of the placenta, and significantly increased the incidence of intrauterine deaths. The high incidence of fetal death and fetal risk attributable to a placental fault in our series suggest that a similar change may occur in pregnant women. (Warrell, D.W. et al. 1968)
CASE REPORT STUDY - From 18 case reports, there were 26 exposed pregnancies of which 7 (27%) ended with malformed offspring (higher than the usually reported population frequency of about 3%). Among them, 4 (15%) were cleft palate (Doig and Coltman, 1956; Bongiovanni and McPadden, 1960; Harris and Ross, 1956). that is, they may have been more likely to be reported because the association with cleft palate in mice was known. The other malformations were bilateral nuclear cataract, gastroschisis, and hydrocephalus. This fact could signify a teratogenic effect, or result from reporting bias.
In addition, they reviewed 17 reported series of 457 mothers exposed to corticosteroids in the first trimester. In this group, 16 (3.5%) of the offsprings were malformed, rates not higher than the rates observed in the general population. (Fraser, F.C. et al. 1995)
Prednisolone was classified in the FDA pregnancy category C. Risk factor D if used in the 1st trimester.
The Michigan Medicaid surveillance study surveyed 143 newborns exposed to prednisolone of completed pregnancies conducted from 1985 and 1992. Newborns were exposed to prednisolone in the 1st trimester of pregnancy (Rosa, F., personal communication, FDA, 1993). Observed versus expected major malformations was 11/6 (7.7%). The data should support an association between prednisolone and congenital defects. (Briggs, G.G. et al. 2008)
Justification for classification or non-classification
Additional information
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.