Registration Dossier

Administrative data

Description of key information

There were no deaths in acute toxicity tests with Santicizer 261, either in rats (oral, given up to 15.8 g/kg bw) or rabbits (dermal, 24-hour application of up to 7.94 g/kg bw). Studies only available in a brief summary report (reliability code 4), but data considered adequate for assessment. Results indicate that S261 does not need to be classified for acute toxicity. Additional acute toxicity data on high molecular-weight phthalates provide support for this conclusion (OECD, 2004. Draft SIDS Initial Assessment Report on High Molecular Weight Phthalate Esters (HMWPE) category). 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only available as a brief summary report
Qualifier:
no guideline followed
Principles of method if other than guideline:
A total of five rats were administered the test material orally at one high dose and assessed for toxic symptoms.
GLP compliance:
not specified
Test type:
other: Single dose acute oral study
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Average of 215 g for males and 225 g for females
no further data

Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Doses:
15.8 g/kg bw
No. of animals per sex per dose:
2 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic evaluation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 800 mg/kg bw
Remarks on result:
other: No deaths seen at 15.8 g/kg bw
Clinical signs:
Reduced appetite and and activity seen on days one and two after dosing.
Gross pathology:
Viscera appeared normal
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
No deaths were seen in five rats (mixed sex) given a single oral administration of undiluted Santicizer 261 at 15.8 g/kg bw.
Executive summary:

Undiluted Santicizer 261 was orally administered to two male and three female Sprague-Dawley rats at 15.8 g/kg bw. The animals were assessed for toxic symptoms, and the survivors sacrificed 14 days after dosing and examined macroscopically.

All five animals survived the 14-day observation period. Reduced appetite and activity were seen for one to two days (numbers of animals not given). At necropsy, the viscera of all animals appeared normal. The investigators concluded that the LD50 was greater than 15.8 g/kg bw. Under the EU CLP regulations, this study would indicate that Santicizer 261 is not classified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
15 800 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only available as a brief summary report
Qualifier:
no guideline followed
Principles of method if other than guideline:
In an acute dermal toxicity study, the test material was applied to the skin of rabbits at two doses, and animals assessed for toxic symptoms.
GLP compliance:
not specified
Test type:
other:
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.2-2.5 kg
no further data
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
5.01 and 7.94 g/kg bw
No. of animals per sex per dose:
One male was tested at 5.01 g/kg bw, and one male and one female at 7.94 g/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic evaluation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 940 mg/kg bw
Remarks on result:
other: No deaths at 7.94 g/kg bw
Mortality:
All three animals survived the 14-day observation period
Clinical signs:
Reduced appetite and activity seen for one to three days (number of animals and doses not given)
Body weight:
no data
Gross pathology:
The viscera appeared normal following macroscopic examination
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
There were no deaths when three rabbits (mixed sex) were given a 24-hour skin application of undiluted Santicizer 261 at up to 7.94 g/kg bw and then observed for two weeks.
Executive summary:

Undiluted Santicizer 261 was applied to the skin of a total of three New Zealand white rabbits. One male was dosed at each of 5.01 and 7.94 g/kg bw, and one female dosed at 7.94 g/kg bw, for an exposure period of 24 hours. The animals were assessed for toxic symptoms during the observation period, and the surviving animals sacrificed 14 days after dosing and examined macroscopically.

 

All three animals survived the 14-day observation period. Reduced appetite and activity was seen for one to three days (no details on number of animals or doses given). At necropsy, the viscera appeared normal. The investigators concluded that the LD50 was greater than 7.94 g/kg bw. Under the EU CLP regulations, this study would indicate that Santicizer 261 is not classified for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
7 940 mg/kg bw

Additional information

Two acute toxicity studies have been conducted on Santicizer 261, one oral and one dermal (Younger Laboratories, 1976a,b). Although details of the two studies are only available in a brief summary report (hence they have been assigned reliability code 4), the data are considered adequate for assessment.

The oral administration of undiluted Santicizer 261 to two male and three female Sprague-Dawley rats at 15.8 g/kg bw resulted in reductions in appetite and activity for 1-2 days after dosing, but all five rats survived the 14-day observation period. At necropsy, the viscera of all animals appeared normal. The investigators concluded that the oral LD50 was greater than 15.8 g/kg bw.

The 24-hour dermal application of undiluted Santicizer 261 to three New Zealand white rabbits, at doses of 5.01 g/kg bw (one male) and 7.94 g/kg bw (one male and one female) resulted in reductions in appetite and activity for 1-3 days, but all three rabbits survived the 14-day observation period. At necropsy, the viscera of all animals appeared normal. The investigators concluded that the dermal LD50 was greater than 7.94 g/kg bw.

Additional acute toxicity data on high molecular-weight phthalate esters (HMWPE) indicate that these compounds (with a carbon backbone of C7 or greater) are of a low order of acute toxicity by the oral, dermal and inhalation routes of exposure, with LD50/LC50 values of all tested substances exceeding the maximum amounts that can be administered to test animals (OECD, 2004. Draft SIDS Initial Assessment Report on High Molecular Weight Phthalate Esters (HMWPE) category).

Justification for classification or non-classification

Two studies on Santicizer 261 (which are only available in a brief summary report, reliability code 4) are considered adequate for concluding that the substance does not need to be classified for acute oral or dermal toxicity, under the EU CLP regulations.