Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD TG 402, EPA TG OPPTS 870.1200 and in accordance with the Principles of Good Laboratory Practice (GLP)
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2012

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:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
5471-76-3
IUPAC Name:
5471-76-3
Constituent 2
Chemical structure
Reference substance name:
2-butoxyethyl benzoate
EC Number:
226-685-8
EC Name:
2-butoxyethyl benzoate
Cas Number:
5451-76-3
Molecular formula:
C13H18O3
IUPAC Name:
2-butoxyethyl benzoate
Test material form:
other: variable coloured liquid
Details on test material:
- Name of test material (as cited in study report): Butyl Cellosolve™ Benzoate
- Physical state: variable coloured liquid
- Analytical purity: 99.86%
- Lot/batch No.: 02112012-JLT
- Expiration date of the lot/batch: 11 February 2013
- Storage condition of test material: Ambient (+18 to +36 ºC)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: inhouse bred (outbred)
- Age at study initiation: 11-12 weeks
- Weight at study initiation: males - 242.6 - 266.2 g, females - 211.6 - 222.3 g
- Housing: Rats were housed individually in standard polysulfone cages (Size: approximately L 425 x B 266 x H 175 mm), with stainless steel top grills having facilities for pelletted food and drinking water
- Diet (ad libitum): Ssniff® rats / mice pellet food - maintenance meal manufactured by Ssniff Spezialdiäten GmbH., Ferdinand-Gabriel-Weg 16, D-59494 SÖest, Germany, was provided to the animals.
- Water (ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai 400 001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes. The water bottles were replenished once daily and the water bottles were changed once a week.
- Acclimation period: 5-7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22°C
- Humidity (%): 56 - 66 %
- Air changes (per hr): 12 - 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours prior to treatment, the hair on the dorsolateral thoracic surface of the skin was clipped (approximately 8 x 10 cm) with an electric clipper (Aesculap® - Germany).
Based on the individual body weight the undiluted test substance at the dose of 2000 mg/kg body weight [1.97 mL/kg based on the density of the test substance of 1.0164 g/mL] was applied directly to the dorsolateral thoracic surface of the skin of the animal to cover about 10% of body surface and covered with cotton gauze (size: Males: 9 x 6 cm; Females: 8 x 5 cm of 6 ply gauze) and secured in position by nonallergenic surgical tape wound around the torso. The test substance was in contact with the skin for 24 hours.
After the 24-hour contact period, the patches were removed and the application sites were wiped with wet clean towels to remove any residual test substance.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males + 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs of toxicity five times during day 1 (day of administration) i.e., at about 30 minutes, 60 minutes (post administration) and subsequently three times at hourly intervals and once daily during days 2 - 15. Individual body weights of animals were recorded on test days 1 (pre-application), 8 (7 days post application), and 15 (14 days post application).
- Necropsy of survivors performed: yes - At the end of the observation period, all rats were euthanised using isoflurane anaesthesia followed by exsanguination. The external surface of the body, all orifices, tissues and organs of the thoracic and abdominal cavities of all animals were examined for gross pathological changes. All findings were recorded.
- Other examinations performed: The site of application was observed for skin reactions once daily during the 14-day observation period.
Statistics:
None

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Under the conditions of this study, the acute dermal LD50 of 2-butoxyethyl benzoate is greater than 2000 mg/kg body weight in male and female Wistar rats.
Mortality:
There were no mortality observed during the study.
Clinical signs:
There were no clinical signs of toxicity or mortality observed during the study.
Body weight:
All rats gained body weight throughout the observation period.
Gross pathology:
There was no abnormality detected at the necropsy.
Other findings:
There were no skin reactions observed at the site of application.

Any other information on results incl. tables

None

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 acute dermal LD50 of 2-butoxyethyl benzoate was greater than 2000 mg/kg body weight in male and female Wistar rats. According to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will not be classified.
Executive summary:

An acute dermal toxicity test was conducted with male and female Wistar rats to determine the potential for 2-butoxyethyl benzoate to produce toxicity from a short term exposure via the dermal route.

Based on the individual body weight the undiluted test substance at the dose of 2000 mg/kg body weight was applied directly to the dorsolateral thoracic surface of the skin of the animal to cover about 10% of body surface and covered with cotton gauze (size: Males: 9 x 6 cm; Females: 8 x 5 cm of 6 ply gauze) and secured in position by non-allergenic surgical tape wound around the torso. After a 24 -hour contact period with the skin, the unabsorbed test substance at the site of application was removed by wiping with a wet clean towel.

The test was initiated with five female rats at the dose of 2000 mg/kg body weight. As there were no clinical signs of toxicity, local skin reactions or mortality, the treatment was then conducted in 5 male rats at the same dose. All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. There were no clinical signs of toxicity, local skin reactions or mortality. All animals had gained body weight during the 14- day observation period. At the end of observation period, all animals were euthanized and subjected to necropsy. There were no gross pathological abnormalities detected at the necropsy.

Under the conditions of this study, the acute dermal LD50 of 2-butoxyethyl benzoate was greater than 2000 mg/kg body weight in male and female Wistar rats. According to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will not be classified.