Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 August 2014 to 04 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 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, 12 Nousan, Notification No 8147
Deviations:
no
GLP compliance:
yes
Test type:
standard acute 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:
male/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 10 weeks old
- Weight at study initiation: Males 276 to 295 g; females 185 to 207 g. Body weight variation did not exceed ± 20 % of the sex mean.
- Fasting period before study: No
- Housing: During acclimatisation, animals were group housed (cage height 18 cm). During the study, animals were individually housed 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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: One day before exposure (Day -1) an area of approximately 5 x 7 cm on the back of each animal was clipped.
- % coverage: The test material was applied on an area of approx. 10 % of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The test material was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminium foil and elastic bandage. A piece of tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST MATERIAL
- Washing (if done): Dressings were removed and the skin cleaned of residual test material using tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2.073 mL/kg body weight. Dose volume calculated as dose level (g/kg) / density (g/mL).
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
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.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea (eye or snout) was noted in the majority of animals. One animal (No. 1) showed chromodacryorrhoea of the left eye before dosing.
General erythema, erythema maculate, fissures, scales and/or scabs were seen in the treated skin-areas, left hindleg or left flank of the animals during the observation period.
Body weight:
All animals showed bodyweight loss or reduced bodyweight gain (two females) between Days 1 and 8. The changes noted in body weight in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 1: Body Weight Data (g)

Dose Group

Animal Number

Day 1

Day 8

Day 15

Males dosed with 2000 mg/kg bw

1

276

266

293

2

294

291

318

3

290

273

310

4

286

283

299

5

295

284

316

Mean (SD)

288 (8)

279 (10)

307 (11)

Females dosed with 2000 mg/kg bw

6

191

183

188

7

207

191

206

8

202

207

220

9

190

184

184

10

185

189

199

Mean (SD)

195 (9)

191 (10)

199 (14)

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 established to exceed 2000 mg/kg bw.
Executive summary:

The potential of the test material to cause acute dermal toxicity in the rat was investigated in accordance with the standardised guidelines OECD 402, EU Method B.3, EPA OPPTS 870.1200 and JMAFF 12 Nousan, Notification No. 8147 under GLP conditions.

The test material was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. After the exposure period, dressings were removed and the skin cleaned of residual test material using tap water. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15)

No mortality occurred. Chromodacryorrhoea (eye or snout) was noted in the majority of animals. One animal (No. 1) showed chromodacryorrhoea of the left eye before dosing. General erythema, erythema maculate, fissures, scales and/or scabs were seen in the treated skin-areas, left hindleg or left flank of the animals during the observation period.

All animals showed bodyweight loss or reduced bodyweight gain (two females) between Days 1 and 8. The changes noted in body weight in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.

Under the conditions of this study the LD50 value was found to exceed 2000 mg/kg bw.