Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Adequate substance specific and read across data are available for assessing the acute toxicity potential of Santicizer P1700. No adverse effects were observed when P1700 was administered orally to rats or dermally to rats and rabbits.

Acute oral LD50: >2000 mg/Kg bw

Acute dermal LD50: >2000 mg/Kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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
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
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:
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.
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.
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

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

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.

Endpoint:
acute toxicity: oral
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
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
A total of ten rats were administered the test material at several doses by stomach tube and assessed for toxic symptoms and weight gain.
GLP compliance:
not specified
Test type:
other: Range finding acute oral toxicity study
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 220-255 g
no further data


Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2.0, 3.16, 5.01, 7.94, 12.6 and 15.8 g/kg bw
No. of animals per sex per dose:
1 female at each of 2.0, 5.01 and 12.6 g/kg bw, 1 male at each of 3.16 and 7.94 g/kg bw, and 2 females and 3 males at 15.8 g/kg bw.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 9 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic evaluation
Statistics:
No data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 800 mg/kg bw
Remarks on result:
other: No deaths seen at up to 15800 mg/kg bw
Mortality:
All rats survived, and were sacrificed nine days after dosing
Clinical signs:
other: Reduced appetite and slight weakness seen for one to three days (numbers of animals and doses not given)
Gross pathology:
At necropsy, two rats had haemorragic areas in the lungs, and all 6 rats receiving 12.6 g/kg bw and above had gaseous intestinal tracts. The viscera of animals receiving up to 7.84 g/kg bw appeared normal
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
No deaths were seen in ten rats (mixed sex) given a single administration of undiluted Santicizer 278 by stomach tube at up to 15.8 g/kg bw.
Executive summary:

Undiluted Santicizer 278 was administered to Sprague-Dawley rats (of either sex) by stomach tube at 2.0, 3.16, 5.01, 7.94 or 12.6 g/kg bw, and to 5 rats (3 male and 2 female) at 15.8 g/kg bw. The animals were assessed for toxic symptoms and weight gain during the observation period, and the surviving animals were sacrificed nine days after dosing and examined macroscopically.

 

All ten animals survived the nine day observation period. Reduced appetite and slight weakness were seen for one to three days (numbers of animals and doses not given), whilst weight gain was described as "near normal". At necropsy, two rats had haemorragic areas in the lungs, and all 6 rats receiving 12.6 g/kg bw and above had gaseous intestinal tracts. The viscera of animals receiving up to 7.84 g/kg bw appeared normal. The investigators concluded that “the compound was classed as practically non-toxic by oral ingestion in male and female rats”. Under the conditions of this study, the acute oral LD50 can be considered greater than 2 g/kg bw (but likely much higher). Under the EC CLP regulations, this study would indicate that Santicizer 278 is not classified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Adequate

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with Column 2 (Specific Rules for Adaptation), Annex VIII of REACH, testing of P1700 by the inhalation route is not considered necessary because exposure of humans via inhalation is unlikely, taking into account the low vapour pressure of other phthalates and the low likelihood of exposure to aerosols, particles or droplets of an inhalable size.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 June 2015 to 16 September 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal 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 negligble. Each animal received a dose based on their individual body weight.
Principles of method if other than guideline:
Deviation to the Protocol
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.

Amendment to the Protocol
At the request of the Sponsor, additional analysis was conducted according to the current Globally Harmonized System of Classification and Labeling of Chemicals.
The animal supplier, Charles River, was clarified in the protocol subsequent to study initiation.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test Animals
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 male and five healthy, non-pregnant and nulliparous female Sprague-Dawley rats were randomly assigned to the treatment groups.

The animals were born 23 Mar 2015, 13 Apr 2015 and 20 Apr 2015. The pretest body weight range was 243 - 285 g for males and 204 - 223 g for females.

The animals were identified by an indelible body mark and individually housed in suspended wire cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat Chow (Diet #5012) was provided daily. Water was available ad libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Site Preparation
The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The clipped area began at the shoulders and extended to the hipbone and half way down the flank of each side of the animal. The prepared site was approximately 10% of the body surface and remained intact.

Dosing
A single dose of the test article was applied to the prepared site, over a porous gauze dressing at a dose level of 2000 mg/kg. The dose was based on the sample weight as calculated from the specific gravity. The torso was covered with a piece of porous dressing (semi-occlusive) to retain the gauze patch and was secured with non-irritating tape. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gently washing with distilled water.
Duration of exposure:
24 hours
Doses:
Test article applied unchanged (100% concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Type and Frequency of Observations
In vivo
- The test sites were scored for dermal irritation at 24 hours postdose and on Day 14 using the numerical Draize scoring code below. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.

Erythema and Eschar
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1.0 mm) 3
Severe edema (raised more than 1.0 mm, extending beyond the area of exposure) 4

Type and Frequency of Observations (continued)
The animals were observed 1and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects.

Body weights were recorded pretest, weekly and at termination.

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

Analysis of Data
An estimate of the LD50 was made based on mortality occurring during the study. Analysis was conducted according to the current Globally Harmonized System of Classification and Labeling of Chemicals.
Statistics:
None - N/A
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat. (total fraction)
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
All five male and all five female rats survived the 2000 mg/kg 24-hour dermal exposure.
Clinical signs:
other: Dermal Observations At 24 hours post-dosing, erythema was absent to well-defined and edema was absent. By Day 14, erythema was absent to very slight and edema was absent; flaking skin was observed. Systemic Observations Abnormal physical signs including
Gross pathology:
Gross necropsy of all animals revealed no observable abnormalities.

Table 1. Body Weights and Dose Volume

Animal No.

Sex

Dose Volume (mL)

Body Weight (g)

Day 0

Day 7

Day 14

1

Male

0.43

243

273

307

2

Male

0.45

252

288

326

3

Male

0.46

258

295

331

4

Male

0.46

257

285

314

5

Male

0.51

285

334

385

Mean

259

295

333

S.D.

15.7

23.2

30.8

#

5

5

5

 

6

Female

0.37

207

211

213

7

Female

0.40

223

238

244

8

Female

0.39

217

234

252

9

Female

0.37

204

219

224

10

Female

0.39

218

231

234

Mean

214

227

233

S.D.

8.0

11.2

15.5

#

5

5

5

Table 2. Dermal Observations

Time Periods

Animal Number and Sex

Male

Female

1

2

3

4

5

6

7

8

9

10

24-hour

Erythema

0

0

0

0

0

0

1

2

2

1

Edema

0

0

0

0

0

0

0

0

0

0

Day 14

Erythema

0

0

0

0

0

0

0

0

1, f

0

Edema

0

0

0

0

0

0

0

0

0

0

f = flaking skin

Table 3. Necropsy Observations

Animal Number

1

2

3

4

5

6

7

8

9

10

Sex

Male

Female

Death (D) /

Sacrifice (S)

S

S

S

S

S

S

S

S

S

S

Observation

 

Appeared normal /

No findings

X

X

X

X

X

X

X

X

X

X

X: Observed


Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the results observed, the dermal 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.
Executive summary:

A key EPA Guideline OPPTS 870.1200 study was conducted to determine the potential for toxicity of the test material (Santicizer P1700) when applied dermally. Five male and five female Sprague-Dawley rats were dosed dermally with Santicizer P1700 at 2000 mg/Kg of body weight. The test material was kept in contact with the skin for 24 hours and dermal responses recorded at 24 hours post exposure and on Day 14. Animals were observed for toxicity and pharmacological effects at 1 and 4 hours post exposure and once daily for 14 days. Body weights were recorded pretest, weekly and at termination and all animals were examined for gross pathology.

 

No mortality was observed through the study period and abnormal physical signs such as chromorhinorrhea, wetness and soiling of the anogenital area, erythema on the ears and partially chewed food on the cage pan liner were observed. At 24 hours post exposure, erythema was absent to well-defined and edema was absent. By Day 14, erythema was absent to very slight and edema was absent; flaking skin was observed. All animals in both sexes gained body weight by study termination and gross necropsy revealed no remarkable findings.

 

Based on the results observed, the dermal 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.

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
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
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
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
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
Key result
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
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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Adequate for assessment

Additional information

Acute Oral Toxicity

The potential for oral acute toxicity of the test material Santicizer Platinum P1700 was determined according the OECD 425 and OPPTS 870.1000 Testing Guidelines. Five female Sprague Dawley rats were dosed orally with 2000 mg/Kg of Santicizer Platinum P1700 (MB Research Laboratories, 2015a). The single dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle.

The animals were observed for mortality, body weight changes, general toxicity and pharmacological effects. All animals survived until the end of the treatment. No abnormal physical signs nor changes in body weights related to the treatment were observed. The gross pathology was normal. Based on the results of this study, the acute oral LD50 was considered to be greater than 2000 mg/Kg bw.

Read across data is also available from the source dossier that tested Santicizer S278 (benzyl 3-(isobutyryloxy)-1-isopropyl-2,2-dimethylpropyl phthalate) based on analogue read across. A discussion and report on the read across strategy is provided as an attachment in Section 13 of the dossier.

The oral administration of undiluted Santicizer 278 to Sprague-Dawley rats (of either sex) by stomach tube at 2.0, 3.16, 5.01, 7.94 or 12.6 g/kg bw, and to 3 male and 2 female rats at 15.8 g/kg bw resulted in reductions in appetite and slight weakness for 1-3 days after dosing, but all ten animals survived the 9-day observation period. At necropsy, two rats had haemorrhagic areas in the lungs, and all 6 rats receiving 12.6 g/kg bw and above had gaseous intestinal tracts. The viscera of animals receiving up to 7.84 g/kg bw appeared normal. The investigators concluded that the oral LD50 was greater than 15.8 g/kg bw (Younger Laboratories 1969a).

Acute Dermal Toxicity

A key EPA Guideline OPPTS 870.1200 study (MB Research Laboratories, 2015b) was conducted to determine the potential for toxicity of the test material (Santicizer P1700) when applied dermally. Five male and five female Sprague-Dawley rats were dosed dermally with Santicizer P1700 at 2000 mg/Kg of body weight. The test material was kept in contact with the skin for 24 hours and dermal responses recorded at 24 hours post exposure and on Day 14. Animals were observed for toxicity and pharmacological effects at 1 and 4 hours post exposure and once daily for 14 days. Body weights were recorded pretest, weekly and at termination and all animals were examined for gross pathology.

 

No mortality was observed through the study period and abnormal physical signs such as chromorhinorrhea, wetness and soiling of the anogenital area, erythema on the ears and partially chewed food on the cage pan liner were observed. At 24 hours post exposure, erythema was absent to well-defined and edema was absent. By Day 14, erythema was absent to very slight and edema was absent; flaking skin was observed. All animals in both sexes gained body weight by study termination and gross necropsy revealed no remarkable findings.

 

Based on the results observed, the dermal LD50of 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.

Read across data is also available from the source dossier that tested Santicizer S278 (benzyl 3-(isobutyryloxy)-1-isopropyl-2,2-dimethylpropyl phthalate) based on analogue read across. A discussion and report on the read across strategy is provided as an attachment in Section 13 of the dossier.

The covered 24-hour dermal application of undiluted Santicizer 278 to the intact skin 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) resulted in reductions in appetite at 6.31 or 10 g/kg bw and slight weakness for two days at the highest dose, but all five 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 10 g/kg bw (Younger Laboratories, 1969b).

Acute Inhalation Toxicity

There is no acute inhalation toxicity data available for P1700. However, the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

P1700 is not classified for acute lethality by the oral or dermal routes of exposure under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. For non-EU countries, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) defines a fifth category for acute toxicity for chemicals with oral and dermal LD50 values between 2000 and 5000 mg/Kg/bw. Based on the results of available acute oral and dermal toxicity studies, P1700 meet the criteria for a Category 5 classification under UN GHS for acute oral and dermal toxicity.