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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02/02/1982 to 29-05-1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study not conducted to current guideline, however study is scientifically sound and acceptable for assessment.The results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No.1272/2008 (EU CLP) and is therefore suitable for use as a key study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: EPA US Guidelines: Hazard Evaluation: Human and Domestic Animals, Fed. Reg. 43:163, 37336-37402 (1978)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
no
Remarks:
study was conducted in compliance with RTL quality assurance practices, RTL Standard Operating Procedures, and Good Laboratory Practices.
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Pentacalcium hydroxide tris(orthophosphate)
EC Number:
235-330-6
EC Name:
Pentacalcium hydroxide tris(orthophosphate)
Cas Number:
12167-74-7
Molecular formula:
Ca5HO13P3
IUPAC Name:
Calcium hydroxycalcium(1+) phosphate (4:1:3)
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan
- Age at study initiation: no data
- Weight at study initiation: The males ranged between 173-219 grams and the females were between 146-173 grams.
- Fasting period before study: Yes; no food 16-18 hours prior to treatment.
- Housing: five per cage in suspended mesh-bottom plastic cages (19" x 10.5" x 8")
- Diet: Purina Rat Chow provided ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature: 66-72°F (18.9 - 22.2°C)
- no other data on conditions.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

DOSAGE PREPARATION: The test material was suspended in corn oil after it was passed through a #300 mesh screen.
Doses:
5000 mg/kg bw
Control rats received an equivalent dose of corn-oil only.
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: The animals were observed for at least 14 days post treatment for mortality and signs of toxicity.
- Necropsy of survivors performed: Necropsies were performed on any animals that died and on all survivors.
- Observations for clinical signs and mortality will be recorded frequently the first day, and early morning and late afternoon thereafter. These animals will be observed once a day during weekends and holidays. All clinical signs will be recorded as to their onset, duration, and severity. The rats will be weighed on days 0 (prior to treatment), 7, 14, or at death.

Statistics:
no applicable

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the treatment or post exposure periods.
Clinical signs:
Normal behaviour was reported throughout the study for all animals. The only adverse clinical sign observed in male rats was piloerection (until day 2). In female rats adverse clinical signs included depression, piloerection, and diarrhea. All female rats appeared normal by day 1.
Body weight:
There were no adverse effects on bodyweight gain. See Tabes 1-4.
Gross pathology:
Autopsy revealed no abnormalities.

Any other information on results incl. tables

Table 1. Changes in body weight recorded for the female control group

Animal No.*

Volume dosed

Time dosed

Daily bodyweight (grams) on day:

0

7

14

1

4.2

11:00

214

310

358

2

3.9

196

271

310

3

3.7

187

270

321

4

4.0

198

279

321

5

4.1

203

291

342

6

3.8

190

273

324

7

3.7

183

270

333

8

3.6

179

251

311

9

3.5

173

251

302

10

3.6

179

266

319

*Animals 1-5 were in cage A and animals 6-10 were in cage B.

Table 2. Changes in body weight recorded for the male group receiving the test material.

Animal No.*

Volume dosed

Time dosed

Daily bodyweight (grams) on day:

0

7

14

1

2.0

11:37

195

269

328

2

2.0

196

269

298

3

1.9

188

275

321

4

2.0

204

293

351

5

2.0

200

277

320

6

2.2

219

307

351

7

2.1

209

292

337

8

2.0

202

290

313

9

2.0

199

271

334

10

2.0

197

294

342

*Animals 1-5 were in cage A and animals 6-10 were in cage B.

Table 3. Changes in bodyweight recorded for the female control group

Animal No.*

Volume dosed

Time dosed

Daily bodyweight (grams) on day:

0

7

14

1

2.9

10:55

146

213

196

2

3.3

166

212

213

3

3.4

171

211

220

4

3.2

163

197

226

5

3.2

159

188

213

6

3.2

161

202

232

7

3.4

168

187

236

8

3.3

165

201

229

9

3.1

156

210

229

10

3.2

158

217

220

*Animals 1-5 were in cage A and animals 6-10 were in cage B.

Table 4. Changes in body weight recorded for the female group receiving the test material.

Animal No.*

Volume dosed

Time dosed

Daily bodyweight (grams) on day:

0

7

14

1

3.4

11:30

169

209

231

2

3.2

164

200

217

3

3.2

163

200

231

4

3.0

152

190

207

5

3.1

157

197

202

6

3.4

173

210

230

7

3.2

163

196

216

8

3.2

161

202

217

9

3.2

161

198

222

10

3.1

154

189

206

*Animals 1-5 were in cage A and animals 6-10 were in cage B.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was found to have an LD50 > 5000 mg/kg bw. Piloerection was reported for one rat after administration, bodyweights were comparable between the control groups and those groups dosed with the test material. At autopsy the animals appeared normal.
In accordance with Regulation (EC) No. 1282/2008 (EU CLP) pentacalcium hydroxide tris(orthophosphate) has not to be classified for acute toxicity via the oral route.