Retinyl propionate

Repeated dose toxicity: oral

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

Test material information

Constituent 1

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.