Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 August 2014 to 02 September 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, 12 Nousan, Notification No 8147
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Benzoic acid, 2-hydroxy-,C14-18 alkyl derivs.
EC Number:
931-472-4
Cas Number:
182700-89-6
IUPAC Name:
Benzoic acid, 2-hydroxy-,C14-18 alkyl derivs.
Test material form:
liquid: viscous
Details on test material:
- Appearance: Clear reddish-brown viscous liquid
- Storage conditions of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Wistar strain Crl:WI (Han) (outbred, SPF-Quality)
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: 151 to 168 g. Body weight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3 to 4 hours after administration of the test material. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labelled cages (height 18 cm) containing sterilised sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24 °C
- Humidity: 40 to 70 % (relative)
- Air changes: at least 10 air changes/hour
- Photoperiod: 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.073 mL/kg bw. The dose volume was calculated as dose level (g/kg) / density (g/mL).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Starting dose = 2000 mg/kg bw. Substance initially assumed to be of low toxicity based on test on amixture containing the substance.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females; the test material was administered to two subsequent groups of three female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed for mortality and viability twice daily. Body weights were recorded on Day 1 (pre-administration of the test material) and on Days 8 and 15. At periodic intervals on the day of dosing (Day 1) and once daily thereafter until Day 15, animals were observed for clinical signs. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed as the method used is not intended to allow the calculation of a precise LD50 value.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and piloerection were noted for all animals between Days 1 and 8. Lethargy and/or lean appearance were noted for one animal on Day 5 and/or 6.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination revealed adhesions between the stomach and diaphragm in all animals.

Any other information on results incl. tables

Table 1: Body Weight Data (g)

Dose Group

Animal Number

Day 1

Day 8

Day 15

First group dosed with 2000 mg/kg bw

1

152

162

176

2

159

179

195

3

168

176

207

Mean (SD)

160 (8)

172 (9)

193 (16)

Second group dosed with 2000 mg/kg bw

4

152

165

197

5

151

170

203

6

155

165

198

Mean (SD)

153 (2)

167 (3)

199 (3)

SD = Standard deviation

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LD50 value was experimentally establised to exceed 2000 mg/kg bw and in accordance with OECD Guideline 423, the LD50 cut-off value was considered to be 5000 mg/kg
Executive summary:

The potential of the test material to cause acute oral toxicity in the rat was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12 Nousan, Notification No. 8147 under GLP conditions.

The test material was administered by oral gavage to two subsequent groups of three fasted female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was conducted after terminal sacrifice (Day 15).

No mortality occurred. Hunched posture and piloerection were noted for all animals between Days 1 and 8. Lethargy and/or lean appearance were noted for one animal on Day 5 and/or 6. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Macroscopic post mortem examination revealed adhesions between the stomach and diaphragm in all animals.

Under the conditions of this study the LD50 value was established to exceed 2000 mg/kg bw and according to OECD Guideline 423 the LD50 cut-off value was considered to be 5000 mg/kg.