Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 July to 25 July 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study carried out according to OECD Guideline 401 (1987); performed according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxypropyl 2-ethylhexanoate
EC Number:
261-499-0
EC Name:
2-hydroxypropyl 2-ethylhexanoate
Cas Number:
58921-10-1
Molecular formula:
C11H22O3
IUPAC Name:
2-hydroxypropyl 2-ethylhexanoate
Constituent 2
Chemical structure
Reference substance name:
1-hydroxypropan-2-yl 2-ethylhexanoate
Molecular formula:
C11H22O3
IUPAC Name:
1-hydroxypropan-2-yl 2-ethylhexanoate
impurity 1
Chemical structure
Reference substance name:
Monoesters of 2-ethylhexanoic acid and dipropyleneglycol
IUPAC Name:
Monoesters of 2-ethylhexanoic acid and dipropyleneglycol
impurity 2
Chemical structure
Reference substance name:
1-methylethylene 2-ethylhexanoate
EC Number:
301-185-3
EC Name:
1-methylethylene 2-ethylhexanoate
Cas Number:
93981-97-6
Molecular formula:
C19H36O4
IUPAC Name:
propane-1,2-diyl bis(2-ethylhexanoate)
impurity 3
Chemical structure
Reference substance name:
2-ethylhexanoic acid
EC Number:
205-743-6
EC Name:
2-ethylhexanoic acid
Cas Number:
149-57-5
Molecular formula:
C8H16O2
IUPAC Name:
2-ethylhexanoic acid
impurity 4
Reference substance name:
Propane-1,2-diol, propoxylated
EC Number:
500-039-8
EC Name:
Propane-1,2-diol, propoxylated
Cas Number:
25322-69-4
IUPAC Name:
Propane-1,2-diol, propoxylated
impurity 5
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Water
Test material form:
liquid: viscous
Specific details on test material used for the study:
Name of test material (as cited in study report): SER-AD FX 511
- Physical state: liquid
- Analytical purity: no data; identity, purity and stability of the test material were the responsibility of the sponsor
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd., Margate, Kent, UK
- Age at study initiation: 5 -8 w
- Weight at study initiation: 145-155 g (males), 135-147 g (females)
- Fasting period before study: overnight before dosing
- Housing: groups of up to five animals of the same sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 47-66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: no vehicle was used; dose volume applied: 2.15 ml/kg
- Rationale for the selection of the starting dose: a range-finding test was conducted initially so as to determine the appropriate dose for the main study. Two animals ( one male, one female) were treated orally by gavage with a dose of 2000 mg/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for mortality and clinical signs of toxicity 0.5, 1, 2 and 4 h post-treatment, and once per day for the whole observation period. Body weights were recorded on day 0, 4, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathological examination
Statistics:
Not used, not necessary for such a type of study.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Range-finding study: no death of animals occured. Hunched posture and lethargy were observed, which returned to normal 1 day post-treatment. Hence, the dose of 2000 mg/kg bw was chosen for the main study.
Main study: no animal died during after administration of the test substance
Clinical signs:
Hunched posture, lethargy and ataxia were observed post-treatment. The animals appeared normal 1 day after dosing. Decreased reaspiratory rate was recorded in one male 2-4 hours after administration of the test material, which was reversible and was not obsevred from day 1 post-treatment onwards. No other signs of systemic toxicity were seen.
Body weight:
The body weight gain of treated animals was not affected by the treatment (see below Table1).
Gross pathology:
No treatment-related abnormalities were detected in any of the animals tested in the post-moterm examinations.
Other findings:
- Organ weights: not recorded
- Histopathology: not performed due to no detected abnormalities in the gross pathological examination

Any other information on results incl. tables

Table 1: Individual body weights and weekly body weigh changes in the main study

Dose level (mg/kg bw)

Animal No

Body weight (g) at day

Body weight gaing (g) during week

0

7

14

1

2

2000

Males

1

146

195

233

49

38

2

145

196

244

51

48

3

155

221

280

66

59

4

155

216

270

61

54

5

155

219

281

64

62

Females

1

135

175

206

40

31

2

142

172

200

30

28

3

145

181

209

36

28

4

147

186

207

39

21

5

141

174

198

33

24

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is of a low order of toxicity following a single oral exposure of rats. The LD50 is >2000mg/kg bw.
Executive summary:

In an acute oral toxicity study, groups of overnight fasted, young adult Sprague-Dawley CD rats 5/sex/dose, were given a single oral dose (by gavage) of 2000 mg/kg bw SER-AD FX 511 (unchanged) and were observed for 14 days. The dose was decided based on a prior-range finding study. The test material was found to be of a low order of acute toxicity following exposure of rats. No mortality was observed. The LD50 for both male and female rats is higher than 2000 mg/kg bw. Clinical signs on the day of dosing included hunched posture, ataxia and lethargy. One animal showed decreased respiratory rate. All clinical symptomps disappeared on day 1 after treatement. All animals except had gained weight 7 and 14 days following dosing. The post-moterm examination revealed no signs of adverse effects. On the basis of this study, SER- AD FX 511 does not warrant classification as being harmful or toxic.