Registration Dossier

Administrative data

Description of key information

For 1-Methyl-1-phenylethyl peroxyneodecanoate (target substance), suitable data are available to assess the acute toxicity. In an acute oral in vivo toxicity study conducted similar to OECD 401, Charles River CD rats (5/sex/dose) were orally exposed to 2034, 3229, 5126, 8137 and 12918 mg/kg bw Cumyl peroxyneodecanoate (target substance, 90.2% purity). In this study, the oral LD50 in rats in considered to be 5126 mg/kg bw. In a second available acute oral in vivo toxicity study conducted according to OECD 401, Sprague-Dawley rats were given a single oral dose of TRIGONOX 99-C75 (target substance, 75% purity). In this study, the oral LD50 in rats is considered to be greater than 2000 mg/kg bw.

In an acute inhalation toxicity study similar to OECD 403, Charles River CD rats were exposed by inhalation route to LUPERSOL 188M75 containing 75.5% cumyl peroxyneodecanoate (0.19% Hydro; 896 ppm Cl-) for 1 hour via whole body exposure at a concentration of 20.4 mg/L. No mortality occurred during the 14-day observation period.

In an acute dermal toxicity study conducted similar to OECD 402, groups of New Zealand White rabbits (three/sex) were dermally exposed to Cumyl peroxyneodecanoate (90.2% purity) for 72 hours at doses of 500, 1250, 3150, 7940 and 19800 mg/kg bw. Based on the results, the dermal LD50 was considered to be within < 19800 and > 7940 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:
weight of evidence
Study period:
1977-09-02 to 1978-02-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name: Cumyl peroxyneodecanoate (SN-1-4462-71)
- Purity: 90.2%
- Appearance: viscous yellowish liquid
Species:
rat
Strain:
other: Charles River CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, Michigan
- Weight at study initiation: 200 - 248 g
- Housing: Animals were housed by sex in groups of 5 rats per cage in hanging wire-mesh cages
- Water: ad libitum
- Diet: ad libitum; Purina Laboratory Chow (withheld during overnight period preceding oral administration)
- Temperature and humidity controlled quarters
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
once (to male and female): 2034, 3229, 5126, 8137, 12918 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

OBSERVATIONS
- Weighing: Initially, at 7 and 14 days
- Mortality/Viability: During first four hours after dosing, at 24 hours and daily thereafter
Statistics:
Statistical Reference
LD50 values and associated 95% confidence interval, slope of dose mortalitiy curve
References:
- Weil, C.S. 1952. Tables for Convenient Calculation of Median Effective Dose and Instruction in Their Use. Biometrics, 8: 249 - 263
- Thompson, W.R. and Weil, C.S. 1952. On the Construction of Tables for Moving Average Interpolation. Biometrics, 8: 51 - 54
- Eby, R. 1957. Statistical Tables for Dose Evaluation, Report No. 5711. Miles - Ames Research Laboratoy, Elkhart, Indiana
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
4 068 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 132 - <= 5 284
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
6 458 mg/kg bw
Based on:
test mat.
95% CL:
>= 5 590 - <= 7 462
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 126 mg/kg bw
Based on:
test mat.
95% CL:
>= 4 294 - <= 6 118
Mortality:
At 8137 and 12918 mg/kg all animals died. At 5126 mg/kg 4/5 female animals were found dead and at 3229 mg/kg 1/5 female animals died. No deaths occured at a dose of 2034 mg/kg.
For individual results see Table 1 in box 'Any other information on results incl. tables'.
Clinical signs:
No data
Body weight:
A trend in decreasing body weight gain is observed in survived animals.
For individual results see Table 1 in box 'Any other information on results incl. tables'.
Gross pathology:
No data

Table 1: Mortality and LD50 Values

Exposure Conc. mg/kg

Number of Deaths

Total Mortalities

 

Postexposure

Hrs.

Days

0 - 4

1

2

3

4

5

6

7 - 14

M

F

M

F

M

F

M

F

M

F

M

F

M

F

M

F

Male

Female

Total

2034

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

0/5

0/5

0/10

3229

 

 

 

 

 

 

 

1

 

 

 

 

 

 

 

 

0/5

1/5

1/10

5126

 

 

 

2

 

2

 

 

 

 

 

 

 

 

 

 

0/5

4/5

4/10

8137

1

3

3

2

 

 

1

 

 

 

 

 

 

 

 

 

5/5

5/5

10/10

12918

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5/5

5/5

10/10

The Acute Oral LD50 Values and 95% Confidence Limits

Male Rats: 6458 (5590 - 7462)

Female Rats: 4068 (3132 - 5284)

Combined Male and Female Rats: 5126 (4294 - 6118)

Slope

Male Rats: 1.66

Female Rats: 1.66

Combined Male and Female Rats: 1.66

Table 2: Body Weights obtained during 14 -day observation period

Dosage Level mg/kg

Individual Rat No.

Sex

Control Weight (grams)

7-Day Weight (grams)

14-Day Weight (grams)

2034

70485

Male

211

295

334

70486

Male

231

272

286

70487

Male

244

312

343

70488

Male

248

296

323

70498

Male

243

291

324

70490

Female

214

248

256

70491

Female

210

243

258

70492

Female

208

242

273

70493

Female

202

247

254

70494

Female

200

224

243

3229

70354

Male

200

258

310

70355

Male

221

245

292

70356

Male

215

281

312

70357

Male

201

264

324

70358

Male

213

280

325

70349

Female

212

234

226

70350

Female

200

240

246

70351

Female

214

238

260

70352

Female

200

Died

Died

70353

Female

216

252

241

5126

70364

Male

200

211

222

70365

Male

201

244

308

70366

Male

205

269

318

70367

Male

202

225

258

70368

Male

207

248

288

70359

Female

200

235

216

70360

Female

200

Died

Died

70361

Female

201

Died

Died

70362

Female

220

Died

Died

70363

Female

210

Died

Died

8137

70374

Male

201

Died

Died

70375

Male

203

Died

Died

70376

Male

208

Died

Died

70377

Male

205

Died

Died

70378

Male

200

Died

Died

70369

Female

210

Died

Died

70370

Female

218

Died

Died

70371

Female

220

Died

Died

70372

Female

206

Died

Died

70373

Female

204

Died

Died

12918

70384

Male

215

Died

Died

70385

Male

200

Died

Died

70386

Male

210

Died

Died

70387

Male

200

Died

Died

70388

Male

200

Died

Died

70379

Female

204

Died

Died

70380

Female

200

Died

Died

70381

Female

210

Died

Died

70382

Female

210

Died

Died

70383

Female

202

Died

Died

 

Interpretation of results:
GHS criteria not met
Conclusions:
The presented studies finds that 1-Methyl-1-phenylethyl peroxyneodecanoate is not of acute oral toxicity and that GHS criteria are not met.
Executive summary:

In a primary acute oral toxicity study (similar to OECD 401), Charles River CD rats (5/sex/dose) were orally exposed to 2034, 3229, 5126, 8137 and 12918 mg/kg bw Cumyl peroxyneodecanoate (1-Methyl-1-phenylethyl peroxyneodecanoate, 90.2% purity), suspended in corn oil. Animals then were observed for 14 days. Due to mortality distribution, the oral LD50 in rats in considered to be 6458 mg/kg bw for males, 4068 mg/kg bw for females and 5126 mg/kg bw for both sexes.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1992-10-9 to 1992-12-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
TEST MATERIAL
- Brand name: TRIGONOX 99-C75
- Batch No. 0509207222002
- CAS No.: 26748-47-0
- Purity: 75% Cumylperoxyneodecanoate in aromatic free mineral spirit (CAS No.: 26748-47-0 and 31807-55-3)
- Appearance: clear colorless liquid

SOURCE OF TEST MATERIAL
- Source and lot/batch No. of test material: Akzo Chemicals International BV, Barcham Wuytierslaan 10, P.O. Box 975, 3800 AZ Amersfoort, The Netherlands; batch-no.: 0509207222002

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: freezer

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was prepared at the appropriate concentration in maize oil.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (U.K.) Limited, Margate, Kent, England
- Age at start of treatment: approx. 5 weeks
- Body weight at start of treatment: males 137 - 149 g, females 128 - 142 g
- Fasting period before study: Food was removed from the hoppers at approx. 15 hours on the day before dosing.
- Identification: tail tattoos
- Acclimatization: at least 5 days
- Housing: Animals were housed in stainless steel grid cages (Stephen Clark Fabrications Limited, Alva, Clackmannanshire, Scotland). The grid floor ensured rapid removal of waste material to undertray. Five animals of the same sex were accommodated in each cage.
- Diet: ad libitum, pelleted rodent diet (RM-1 S.Q.C., from Special Diets Services Limited, Witham, Essex, England); removal of food for approx. 21 hours before administration of test material until 3 hours after administration
- Water: ad libitum, tap water

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 21 °C
- Humidity (%): 36 - 55 % R.H.
- Photoperiod (hrs dark / hrs light): 12/12
- Air changes per hour: 15 (without re-circulation)
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Clinical signs: Day 1: 1 h, 3 h and 5 h post-exposure; daily thereafter; Weighing: day before dosing and Day 1, 8 and 15
- Necropsy of survivors performed: Yes, all animals were sacrificed
- Other examinations performed: no
Statistics:
LD50 values and associated 95% confidence interval
Preliminary study:
Group of one male and one female rat given single oral administration of TRIGONOX 99-C75 at single dosage of 800 mg/kg bw, at constant volume-dosage of 10 mL/kg in maize oil. No deaths occured.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured. See also Table 1 in box 'Any other information on results incl. tables'.
Clinical signs:
Clinical signs as underactivity, staggering gait, piloerection and hunched posture on the day of dosing were observed. The animals were overtly normal by the following day.
For individual results, see Table 2 in box 'Any other information on results incl. tables'.
Body weight:
All animals achieved expected body weight gains.
See Table 4 in box 'Any other information on results incl. tables'.
Gross pathology:
Necropsy on day 15 revealed no significant macroscopic lesion.
See Table 5 in box 'Any other information on results incl. tables'.

Table 1: Mortality

Dosage

(mg/kg bw)

Male

Female

Combined

2000

0/5

0/5

0/5

Table 2: Distribution of signs - MALE

Signs of reaction to treatment

Cage, sex and animal number X651 MALE

Number showing effect at time after dosing

Hour

Day

801

802

803

804

805

1/4

1/2

1

3

5

2

3

4

5

6

7

8

9

10

11

12

13

14

15

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

Decedents: None

Animals survivingat Day 15

No abnormality detected

 

 

 

 

 

5

5

 

 

 

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Underactivity

+

+

+

+

+

 

 

 

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Staggering gait

+

+

+

+

+

 

 

5

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

+

+

+

+

+

 

 

 

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

+

+

+

+

+

 

 

 

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Total number of survivors: 5

+ Indicates an animal exhibiting a sign: a = am; p = pm

Table 3: Distribuion of signs FEMALE

Signs of reaction to treatment

Cage, sex and animal number X651 MALE

Number showing effect at time after dosing

Hour

Day

806

807

808

809

810

1/4

1/2

1

3

5

2

3

4

5

6

7

8

9

10

11

12

13

14

15

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

p

a

Decedents: None

Animals survivingat Day 15

No abnormality detected

 

 

 

 

 

5

5

 

 

 

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Underactivity

+

+

+

+

+

 

 

 2

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Staggering gait

+

+

+

+

+

 

 

5

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Piloerection

+

+

+

+

+

 

 

 

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hunched posture

+

+

+

+

+

 

 

 1

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Total number of survivors: 5

Table 4: Individual body weights

Bodyweight (g)

Animal number and sex

801M

802M

803M

804M

805M

Day

-1

149

137

139

147

141

Day

1

133

123

122

123

121

Day

8

214

192

199

203

189

Day

15

280

256

268

259

255

Increment

131

119

129

112

114

Mean of Increment

 

 

 

 

121

 

806F

807F

808F

809F

810F

Day

-1

128

137

142

138

130

Day

1

116

119

127

121

117

Day

8

168

178

193

178

164

Day

15

196

207

223

196

184

Increment

68

70

81

58

54

Mean of increment

 

 

 

 

66

Table 5: Necropsy observation

Aminal number and sex

Died or

Sacrificed

Time of death

Day

Necropsy observation

801M

Sacrificed

15

External: No significant lesion

Internal: No significant lesion

802M

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

803M

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

804M

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

805M

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

806F

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

807F

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

808F

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

809F

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

810F

Sacrificed

15

External: No significant lesion

               Internal: No significant lesion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg bw.
Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 401, fasted Sprague-Dawley rats (5/sex/dose) were given a single oral dose of TRIGONOX 99-C75 (1-Methyl-1-phenylethyl peroxyneodecanoate, 75% purity), suspended in maize oil, at a dose of 2000 mg/kg bw and were observed for 15 days. Due to the absence of mortality and low adverse clinical signs, the oral LD50 in rats is considered to be greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Guideline study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-04-04 to 1978-07-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
1 hour exposure instead of 4 hours
GLP compliance:
not specified
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
- Name of the test material: SN-1-4462-71X
- Chemical name: cumyl peroxyneodecanoate
- Purity: 75.5% (0.19% Hydro, 896 ppm Cl)
- Appearance: pale yellow liquid
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS & ENVIRONMENTAL CONDITIONS
- Source: no data
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: 235-242 g (male rats), 200-214 g (female rats)
- Fasting period before study: no data
- Housing: The rats were housed individually in wire-mesh cages and were kept throughout the pre- and post-exposure periods in a temperature and humidity controlled room in accordance with standards outlined in the "Guide For the Care and Use of Laboratory Animals; DHEW No. (N.I.H. 74-23) 1974". During exposure, the rats were caged individually in compartmented wire-mesh exposure cages. The cages were placed in a 160-liter cubical, stainless steel and glass chamber. A constant chamber airflow was maintained by means of a rotary centrifugal air pump located at the exhaust side of the chamber. The chamber exhaust was filtered with an activated charcoal filter and a Cambridge Absolute® filter before being discharged outside of the laboratory.
- Diet (e.g. ad libitum): Purina Laboratory chow, ad libitum (except in the exposure chamber)
- Water (e.g. ad libitum): ad libitum (except in the exposure chamber)
- Acclimation period: 1 week
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The vapors of the compound were generated by metering the liquid at the rate of 0.494 mL/min with a Harvard Infusion pump into a positive pressure atomizer located near the chamber air inlet at the top of the exposure chamber. An air pressure of 10 psig, with an air-flow rate of 8 L/min, was applied to the atomizer which aerosolized the liquid for rapid vaporization. The vapors and aerosols emerging from the atomizer were diluted by the incoming chamber air at the rate of 14 L/min to the desired concentration. The "metered" concentration of the compound (20.4 mg/L) in the chamber atmosphere was calculated from the ratio of the rate of liquid dissemination (449.5 mg/min*) to the rate of total chamber airflow (22 L/min). The total chamber airflow represents the volume of air ejected from the atomizer plus the volume of make-up air passing through the chamber per unit time.

*The specific gravity of the liquid was gravimetrically determined to be 0.91

Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Concentrations:
20.4 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for toxic signs and mortility were made during and immediately following the 1 hour exposure period and twice daily thereafter for 14 days.
- Frequency of weighing: Individual body weights were recorded prior to the 1 hour exposure and periodically thereafter.
- Necropsy of survivors performed: yes
Statistics:
no data
Preliminary study:
n.a.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20.4 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
None of the rats died in the experiment.
Clinical signs:
The immediate response of the rats to the experimental atmosphere was an increase of activity in preening. After several minutes of exposure, this activity decreased. After 20 minutes of exposure 50% of the rats exhibited slight dyspnea. At 30 minutes, all the rats exhibited slight dyspnea which persisted for the remainder of the exposure period. In addition, a few rats intermittently exhibited salivation. Slight dyspnea was observed in a few rats for 1 to 8 days post-exposure. In addition, one rat exhibited eye squint on day 1 post-exposure.
Body weight:
A slight body weight loss was observed in the rats for 1-5 day post-exposure. By the end of the 14-day post-exposure, the body weights of all the rats exceeded those of the pre-exposure values. See Table 1 in box 'Any other information on results incl. tables'.
Gross pathology:
Gross pathological examination of the rats which were sacrificed at the end of the experimental period revealed gray patches on the lungs of 1 male rat and no compound related pathologic changes in the remaining 9 rats.

Table 1: Individual Body Weights

Individual body weights (in grams)
Pre-exposure Post-exposure (Days)
0 1 3 5 7 14
Rat no. Sex
1 M 235 220 232 262 286 346
2 M 240 225 240 260 285 328
3 M 238 224 236 258 276 320
4 M 235 221 238 258 271 300
5 M 242 224 236 255 272 295
6 F 200 192 200 211 218 236
7 F 200 202 205 212 226 228
8 F 210 192 222 211 224 240
9 F 214 200 210 220 229 250
10 F 210 199 200 207 224 232
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute inhalation study, Charles River CD rats were inhaled via whole-body exposure to 20.4 mg/L for 1 hour. No mortality occurred during the 14-day observation period. Based on the results, the LC50 is considered to be greater than 20.4 mg/L.
Executive summary:

In an acute inhalation toxicity study conducted similar to OECD 403, groups of Charles River CD rats (5/sex) were exposed by inhalation route to LUPERSOL 188M75 containing 75.5% cumyl peroxyneodecanoate (0.19% Hydro; 896 ppm Cl-) for 1 hour to whole body at a concentration of 20.4 mg/L. Animals then were observed for 14 days. No mortality occurred. During exposure, animals showed an increase of activity in preen in and all rats exhibited slight dyspnea and some rats exhibited salivation. One rat exhibited eye squint on day 1 post-exposure. A slight body weight loss was observed in the rats for day 1 to 5 post-exposure. In one male rat, grey patches on the lungs were observed. Based on the results, the LC50 is greater than 20.4 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Comparable to guideline study

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
Study period:
1977-09-02 to 1978-02-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 2 animals per dose group were used
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
- Name: Cumyl peroxyneodecanoate (SN-1-4462-71)
- Purity: 90.2%
- Appearance: viscous yellowish liquid
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Pennwalt Corporation (Lucidol Division), Buffalo, New York
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sweetwater Farm, Hillsboro, Ohio
- Weight: 2343 - 3000 g
- Housing: Animals were housed individually in hanging wire-mesh cages
- Water: ad libitum
- Diet: ad libitum; Purina Rabbit Chow
- Temperature and humidity controlled quarters
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
The hair was removed from the back of each rabbit (20 – 30% of the body surface) with an electric clipper. The test material
Duration of exposure:
24 h
Doses:
500, 1250, 3150, 7940 and 19800 mg/kg bw
No. of animals per sex per dose:
1 male and 1 female rabbits
Control animals:
no
Details on study design:
TEST SITE
- Area of exposure: Back; on 20-30% of the body surface the hair was removed.
- % coverage:
- Type of wrap if used: The area of application was wrapped with gauze bandaging and occluded with Saran Wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with tepid tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Dose volume: 500, 1250, 3150, 7940 and 19800 mg/kg
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 940 - < 19 800 mg/kg bw
Based on:
test mat.
Mortality:
The two rabbits at the 19800 mg/kg dosage level died. None of the other rabbits died during the 14-day observation period.
Clinical signs:
No data
Body weight:
Body weight gain was noted for all surviving animals during the test period, except for one male at 500 mg/kg and one female at 7940 mg/kg bw.
For individual results see Table 1 in box 'Any other information on results incl. tables'.
Gross pathology:
No data

Table 1: Body Weights: The following body weights were obtained during the 14-day observation period

Dosage level mg/kg

Individual rabbit no.

Sex

Control Weight (grams)

7-Day weight (grams)

14-day weight (grams)

500

30237

Male

2575

2693

2508

30238

Female

2720

2844

2978

1250

30331

Male

2955

3038

3215

30254

Female

3000

3226

3465

3150

30259

Male

2841

2835

3081

30340

Female

2786

2665

2946

7940

30339

Male

2770

2668

2874

30338

Female

2446

2251

2326

19800

30327

Male

2669

Died

Died

30336

Female

2343

Died

Died

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, the acute dermal LD50 of 1-methyl-1-phenylethyl peroxyneodecanoate (90.2% purity) was found to be greater than 7940 mg/kg but less than 19800 mg/kg.
Executive summary:

In an acute dermal toxicity study (similar to OECD 402), groups of New Zealand White rabbits (1/sex/dose) were dermally exposed to Cumyl peroxyneodecanoate (90.2% purity) in for 24 hours to 20 – 30% of the body surface at doses of 500, 1250, 3150, 7940 and 19800 mg/kg bw. Animals then were observed for 14 days. Under the conditions of this study, the acute dermal LD50 of 1 -Methyl-1-phenylethyl peroxyneodecanoate was found to be greater than 7940 mg/kg but less than 19800 mg/kg.

Body weight gain was noted for all surviving animals during the test period, except for one male at 500 mg/kg and one female at 7940 mg/kg bw.

No changes in body weight gain was observed. Mortality occurred at the highest dose level (19800 mg/kg bw) in both animals. None of the other rabbits died during the 14-day observation period.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
7 940 mg/kg bw
Quality of whole database:
Comparable to guideline study

Additional information

For 1-Methyl-1-phenylethyl peroxyneodecanoate (target substance), suitable data are available to assess the acute toxicity. In an acute oral in vivo toxicity study conducted similar to OECD 401, Charles River CD rats (5/sex/dose) were orally exposed to 2034, 3229, 5126, 8137 and 12918 mg/kg bw Cumyl peroxyneodecanoate (target substance, 90.2% purity). In this study, the oral LD50 in rats in considered to be 5126 mg/kg bw. In a second available acute oral in vivo toxicity study conducted according to OECD 401, Sprague-Dawley rats were given a single oral dose of TRIGONOX 99-C75 (target substance, 75% purity). In this study, the oral LD50 in rats is considered to be greater than 2000 mg/kg bw.

In an acute inhalation toxicity study similar to OECD 403, Charles River CD rats were exposed by inhalation route to LUPERSOL 188M75 containing 75.5% cumyl peroxyneodecanoate (0.19% Hydro; 896 ppm Cl-) for 1 hour via whole body exposure at a concentration of 20.4 mg/L. No mortality occurred during the 14-day observation period.

In an acute dermal toxicity study conducted similar to OECD 402, groups of New Zealand White rabbits (three/sex) were dermally exposed to Cumyl peroxyneodecanoate (90.2% purity) for 72 hours at doses of 500, 1250, 3150, 7940 and 19800 mg/kg bw. Based on the results, the dermal LD50 was considered to be within < 19800 and > 7940 mg/kg bw.

Justification for classification or non-classification

Based on the available data the target substance 1-metyl-1-phenylethyl peroxyneodecanoate does not warrant classification for acute toxicity. LD50 values for the dermal and oral route were above the limit values of the relevant OECD guidelines. In an acute inhalation study no mortality occurred and the LC50 is considered to be greater than 20.4 mg/L.