Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only available as a brief summary report

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1969
Report date:
1969

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a minimum lethal dose study, the test material was applied to the skin of rabbits at several doses, and animals assessed for toxic symptoms.
GLP compliance:
not specified
Test type:
other:
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of benzyl 1-(isobutyryloxy)-2,2,4-trimethylpentan-3-yl phthalate and benzyl 3-(isobutyryloxy)-2,2,4-trimethylpentyl phthalate
EC Number:
701-008-3
Molecular formula:
C27H34O6
IUPAC Name:
Reaction mass of benzyl 1-(isobutyryloxy)-2,2,4-trimethylpentan-3-yl phthalate and benzyl 3-(isobutyryloxy)-2,2,4-trimethylpentyl phthalate
Constituent 2
Chemical structure
Reference substance name:
Benzyl 3-isobutyryloxy-1-isopropyl-2,2-dimethylpropyl phthalate
EC Number:
240-920-1
EC Name:
Benzyl 3-isobutyryloxy-1-isopropyl-2,2-dimethylpropyl phthalate
Cas Number:
16883-83-3
Molecular formula:
C27H34O6
IUPAC Name:
Benzyl 2,2,4-trimethyl-1-[(2-methylpropanoyl)oxy]pentan-3-yl benzene-1,2-dicarboxylate
Details on test material:
Name of test material (as cited in study report): Santicizer 278
- Lot/batch No.: EL 9026
no further data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0-2.4 kg
no further data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: "plastic strips", evidently to retard evaporation and avoid contamination.
no further data
Duration of exposure:
For periods up to 24 hours
Doses:
2.51, 3.98, 6.31 and 10.0 g/kg bw
No. of animals per sex per dose:
One female at each of 2.51, 6.31 and 10 g/kg bw, and one male at each of 3.98 and 10 g/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weight change assessed 5 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic evaluation
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
All five rabbits survived, and were sacrificed 14 days after dosing
Clinical signs:
Reduced appetite seen for one to three days at 6.31 and 10 g/kg bw, and slight weakness for two days at 10 g/kg bw.
Body weight:
All five rabbits gained between 100 and 200 grams in the 5 days following dosing (about 20 to 40 g/day)
Gross pathology:
The viscera appeared normal following macroscopic examination

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
No deaths were seen in five rabbits (mixed sex) given a covered skin application of undiluted Santicizer 278 at up to 10 g/kg bw, and then observed for two weeks.
Executive summary:

Undiluted Santicizer 278 was applied to the closely clipped, intact skin of a total of five New Zealand white rabbits. Three females were dosed at 2.51, 6.31 or 10 g/kg bw (one at each dose), and two males at 3.98 or 10 g/kg bw. The treated areas were covered with “plastic strips” and the animals held in wooden stocks for periods of up to 24 hours, before being assigned to individual cages. The animals were assessed for toxic symptoms and weight gain during the observation period, and the surviving animals sacrificed 14 days after dosing and examined macroscopically.

All five animals survived the 14-day observation period. Reduced appetite was seen at 6.31 and 10 g/kg bw, and slight weakness for two days at 10 g/kg bw. Growth during the 5 days after dosing appeared unaffected by treatment, and the “viscera appeared normal by macroscopic examination”. The investigators concluded that “the compound was classed as practically non-toxic by skin absorption in male and female rabbits”. Under the conditions of this study, the LD50 can be considered greater than 10 g/kg bw.  Under the EC CLP regulations, this study would indicate that Santicizer 278 is not classified for acute dermal toxicity