Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-08-14 to 1991-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection 1990-05-14
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)
EC Number:
931-276-9
Cas Number:
114959-46-5
Molecular formula:
See information in Section 1.2.
IUPAC Name:
Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)
Details on test material:
- Name of test material (as cited in study report): [CAS Number 114959-46-5]
- Physical state: Clear brown viscous liquid
- Lot/batch No.: 191 (Stanlow); DSP4767/91
- Toxicology reference number: ST91/247
- Stability under test conditions: Stable for the duration of the study under the test conditions employed
- Storage condition of test material: In the dark at ambient temperature under nitrogen
- Date received: 08 August 1991

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 195-219 g (males); 137-155 g (females)
- Fasting period before study: Overnight
- Housing: Single sex groups of up to 5 rats to a cage during quarantine; Single sex groups of up to 3 rats to a cage for at least five days prior to dosing in cages with stainless steel wire-mesh walls floors and tops. Each cage measured 33 cm x 22 cm x 16 cm. Paper-lined trays for excreta were placed beneath each cage and changed three times weekly.
- Diet (e.g. ad libitum): Pelleted diet (LAD 1, Special Diets Services Ltd) ad libitum
- Water (e.g. ad libitum): Water from the public supply ad libitum
- Acclimation period: Minimum of four days quarantine in non-barried animal room with access restricted to essential personnel plus five days acclimation prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 degrees Centigrade with no excursions considered to have influenced the experimental outcome
- Humidity: 30-70 % with no excursions considered to have influenced the experimental outcome
- Photoperiod: 12 hour day and 12 hour night provided by automatically controlled fluorescent lighting


Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before dosing, the dorsal fur was removed from the animals using electric clippers. Any rat showing signs of damage or irritation of the dorsum were replaced. On Day 1 the animals were weighed and a single dose of the undiluted test material was applied to the skin. The test material was held in place with a gauze dressing (approximately 6 x 8 cm) covered with waterproof adhesive tape. The rats were then individually housed. Following exposure the dressings were removed, the skin washed with warm dilute detergent solution, dried and the animals returned to group housing.

Duration of exposure:
24 hours
Doses:
Single dose of 2000 mg/kg administered at a dose volume of 1.90 mL/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Animals assigned to the study were identified by cage labels displaying the animal numbers, experiment number, sex and test material and by ear-notches denoting the animal number.

A detailed clinical examination was made six times on the day of dosing (Day 1) and twice daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 8 and Day 15 bodyweights were recorded and changes in bodyweight calculated.

All animals were subject to necropsy on Day 15. Animals were killed by an intraperitoneal injection of sodium pentabarbitone. External surfaces and orifices were checked and the cranial, thoracic and abdominal cavities and viscera were examined. Any gross pathological changes were recorded.
Statistics:
No data

Results and discussion

Preliminary study:
No data
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died
Clinical signs:
Female rats showed anogenital fur staining (yellow) from Day 2. Recovery was complete by Day 4. Sites of application of the test material were stained brown and, in male rats, had developed erythema by Day 2. The treated skin was overtly normal from Day 4.
Body weight:
All rats had gained weight relative to their Day 1 bodyweights by the end of the 14 day observation period.
Gross pathology:
No macroscopic changes were apparent during necropsy on Day 15.
Other findings:
No data

Applicant's summary and conclusion

Conclusions:
The acute dermal LD50 of the test material in rats was greater than 2000 mg/kg