Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Study period:
09.08.1983 - 19.09.1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The study was performed as a 14-day repeated dose oral toxicity study in mice with daily administration of the substance via gavage. Body weights
were measured but no histopathology and haematology was performed.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Retinyl propionate
EC Number:
230-363-2
EC Name:
Retinyl propionate
Cas Number:
7069-42-3
Molecular formula:
C23H34O2
IUPAC Name:
retinyl propionate
Details on test material:
- Lot/batch No.: 024004
- Stability under test conditions: refrigerator 10°C, protect from light, protect from air

Test animals

Species:
mouse
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 24.25, 48.5, 97.0, 194.0, 388.0 (mg/kg)
Basis:
actual ingested
No. of animals per sex per dose:
6 doses: each 5 females; 5 males
Control animals:
yes, concurrent vehicle
Details on study design:
treatment of controls: peanut oil 5 ml/kg p.o.
Duration of study: 42 days

Results and discussion

Results of examinations

Details on results:
Signs of reaction after dosing: Weight loss, Ataxia, Body sag, Piloerection, Respiratory depression, Cachexia, Hair loss;
Mortalities: Groupe 5: all animals dead after 13th dosing;
Groupe 6: all animals dead after 7th dosing

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Mortalities 28 days after 14th dosing
Groupe
number:		 Dose level
(mg/kg)		 Male Female Total %
1 0 0/5 0/5 0/10 0
2 24.25 0/5 0/5 0/10 0
3 48.5 0/5 0/5 0/10 0
4 97 1/5 0/5 1/10 10
5 194 5/5 5/5 10/10 100
6 388 5/5 5/5 10/10 100

Table 2: Body weight in g +/- SEM (groups means, n = No of animals weighed) 
Groupe
number:		 Dose level
(mg/kg)		 Day of
1st dosing		 Day 1 Day 14 of
observation		 Day 28
1 0 21.0 +/- 0.3
(10)		 31.5 +/- 1.1
(10)		 37.1 +/- 1.2
(10)		 40.9 +/- 1.0
(10)
2 24.25 20.9 +/- 0.3
(10)		 32.1 +/- 1.6
(10)		 38.8 +/- 1.6
(10)		 42.7 +/- 1.8
(10)
3 48.5 20.6 +/- 0.4
(10)		 30.6 +/- 1.3
(10)		 38.7 +/- 1.6
(10)		 41.8 +/- 1.9
(10)
4 97 20.3 +/- 0.3
(10)		 24.6 +/- 1.9
(10)		 33.6 +/- 2.0
(9)		 38.7 +/- 2.1
(9)
5 194 21.0 +/- 0.3
(10)		 _--- _--- _---
6 388 20.7 +/- 0.4
(10)		 _--- _--- _---

Applicant's summary and conclusion

Conclusions:
The LD 50 after repeated oral administrations (once daily on 14 consecutive days) of Vitamin A propionate in mice of both sexes observed over a
period of 28 days was estimated to be 125 (90-175) mg/kg. There were observed signs of hypervitaminosis A.