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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09/06/2015 - 16/09/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
Remarks:
The pretest body weight of Animal 5 exceeded the +/- 20% of the mean body weight by 2 grams. No impact is expected since the degree of weight deviation is negligible. Each animal received a dose based on their individual body weight
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The pretest body weight of Animal 5 exceeded the +/- 20% of the mean body weight by 2 grams. No impact is expected since the degree of weight deviation is negligible. Each animal received a dose based on their individual body weight
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)
EC Number:
950-347-5
Cas Number:
1661012-65-2
Molecular formula:
C27H40O6
IUPAC Name:
1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)
Test material form:
liquid
Specific details on test material used for the study:
Label Identity: Santicizer P-1700
Batch No: VSC1002-2
Supplied by: Valerus Specialty Chemicals
Data received: 12/05/15
Storage: Room temperature and humidity
Description: Clear light-yellow liquid
Specific gravity:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Strain and sex: Sprague-Dawley (5 females)
Age: 2-3 months
Weight: 195-211 g; Weight variation did not exceed ±20% of the mean weight of study animals.
Housing: individually housed by sex in suspended wire cages
Diet: Fresh PMI Rat Chow (Diet # 5012) available ad libitum except for 16-20 hours prior to dosing.
Water: Available ad tibittun, source unspecified.
Acclimation period: At least five days
Pre-test Evaluation: Evaluated for general health and pregnancy status.

Animals were received from Charles River, Stone Ridge NY on 19 May 2015 and 09 Jun 2015. Following an acclimation period of at least five days, five healthy, non-pregnant and nulliparous female Sprague Dawley rats were selected for dosing without conscious bias. The animals were born the on 23 Mar 2015 or 13 Apr 2015. The pretest body weight range was 195-211 grams. The weight variation of the animals used did not exceed ÷ 20% of the mean weight of the previously dosed animals within a sex. The animals were identified by cage notation and indelible body marks, and individually housed in suspended stainless steel wire bottom cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing. Water was available ad libitcim. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12-hour lighudark cycle, and was kept clean and vermin free.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
2000mg/kg bw by syringe and needle orally
Doses:
The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg.
No. of animals per sex per dose:
5 female animals
Control animals:
no
Details on study design:
Dosing
The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg.

Type and Frequency of Observations
Animals were observed at 15 minutes, 1. 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest. weekly and at termination.

Post Mortem — All animals were humanely sacrificed using CO2 following study termination and examined for gross pathology.

Analysis of Data
An estimate of the LD50 was made based on the mortality occurring during the study. Analysis was conducted according to the current Globally Harmonized System of Classification and Labeling of Chemicals
Statistics:
Statistical Analysis: Study data were not analyzed with statistical tests.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 2000 mg/kg oral dose
Clinical signs:
other: No abnormal physical signs were observed among three animals. Partially chewed food was observed in the pan liner of two animals
Gross pathology:
The gross necropsy of all animals revealed no observable abnormalities.
Other findings:
No additional observations

Any other information on results incl. tables

Table 1. Body Weights and Dose Volume

Animal No.

Sex

Dose Volume (mL)

Body Weight (g)

Day 0

Day 7

Day 14

1

Female

0.38

211

236

234

2

Female

0.37

208

234

243

3

Female

0.35

195

212

213

4

Female

0.35

195

218

230

5

Female

0.37

206

253

263

Mean

203

231

237

S.D.

7.5

162

18.3

#

5

5

5

Table 2. Necropsy Observations

Animal Number

1

2

3

4

5

Sex

Female

Female

Female

Female

Female

Death (D) / Sacrifice (S)

S

S

S

S

S

Observation

 

Appeared normal / No findings

X

X

X

X

X

X: Observed

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the results observed, the oral LD50 of Santicizer P1700 was determined to be greater than 2000 mg/Kg of body weight in rabbits. According to GHS Classification, Santicizer P1700 meets the criteria to be classified as Acute Toxic Category 5.
Executive summary:

A key EPA Guideline OPPTS 870.1100 / OECD Guideline 425 study was conducted to determine the potential for toxicity of the test material (Santicizer P1700) when administered orally. Five female Sprague-Dawley rats were administered a single dose of Santicizer P1700 (undiluted) via oral gavage at 2000 mg/Kg of body weight. Animals were observed at 15 minutes, 1, 2 and 4 hours post exposure and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality with body weights recorded immediately pre-test, weekly and at termination. All animals were examined for gross pathology.

 

No mortality was observed through the study period. No abnormal physical signs were observed among three animals while partially chewed food was observed in the pan liner of two animals. All five animals gained body weight by study termination while one animal lost weight from Day 7 to Day 14 of the study period. Gross necropsy revealed no remarkable findings.

 

Based on the results observed, the oral LD50 of Santicizer P1700 was determined to be greater than 2000 mg/Kg of body weight in rats. According to GHS Classification, Santicizer P1700 meets the criteria to be classified as Acute Toxic Category 5.