Santicizer 278®

Acute Toxicity: dermal

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

Test material information

Constituent 1

Reference substance name:

Reaction Mass of Benzyl (1R,1S) 2,2,4-trimethyl-1-[(2-methylpropanoyl)oxy]pentan-3-yl benzene-1,2-dicarboxylate and Benzyl (3R,3S) 2,2,4-trimethyl-3-[(2-methylpropanoyl)oxy]pentyl benzene-1,2-dicarboxylate

EC Number:

701-008-3

Molecular formula:

C27H34O6

IUPAC Name:

Reaction Mass of Benzyl (1R,1S) 2,2,4-trimethyl-1-[(2-methylpropanoyl)oxy]pentan-3-yl benzene-1,2-dicarboxylate and Benzyl (3R,3S) 2,2,4-trimethyl-3-[(2-methylpropanoyl)oxy]pentyl benzene-1,2-dicarboxylate

Constituent 2

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:

other: 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.

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