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Administrative data

Description of key information

The acute oral, inhalation and dermal toxicity studies indicate that the substance is of low  toxicity if swallowed (rat LD0 > or = 2000 mg/kg bw), applied onto the skin (rat LD0 > or = 2000 mg/kg bw) or inhaled (rat LC0> or = 4060 mg/m3 (maximum concentration practicable)).

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:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Table 7.2.1/2: Individual and group mean bodyweights (g) in treated animals during the observation period

Dose mg/kg

Animal n° and sex

Bodyweight (g) at

Day 1 *

Day 8

A

Day 15

B

2000

3F

98

137

(39)

158

(21)

4F

98

135

(37)

153

(18)

5F

97

138

(41)

163

(25)

Mean

98

137

(39)

158

(21)

6M

107

147

(40)

198

(51)

7M

105

151

(46)

197

(46)

8M

106

168

(62)

214

(46)

Mean

106

155

(49)

203

(48)

*: Prior to dosis

Bodyweight gain shown in parenthesis

A: Weight gain on Day 8 B: Weight gain on Day 15

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study complete and sufficient to fulfill the endpoint requirements.

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
Reliability:
1 (reliable without restriction)
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.06 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: maximum practicable concentration

Table 7.2.2/1: Body weights - individual and group mean values (g)

Group

Rat

Day of observation

-6

-3

0

7

14

1M

(control)

1

213

241

263

322

351

2

213

240

257

304

330

3

225

258

281

333

356

4

224

254

277

325

367

5

215

249

271

318

355

Mean

218

248

270

320

352

2M

(treated)

11

213

244

272

310

343

12

221

248

264

298

328

13

212

244

265

308

346

14

216

240

266

294

323

15

216

239

259

291

316

Mean

216

243

265

300

331

1F

(control)

6

200

217

227

325

247

7

201

206

218

225

241

8

199

210

212

225

239

9

203

216

215

231

251

10

209

222

231

240

262

Mean

202

214

221

231

248

2F

(treated)

16

205

209

213

219

224

17

204

219

223

230

252

18

202

206

217

229

242

19

203

210

231

235

241

20

204

214

217

218

231

Mean

204

212

220

226

238

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
4 060 mg/m³
Quality of whole database:
Study complete and sufficient to fulfill the endpoint requirements.

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:
1 (reliable without restriction)
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
other: Directive 92/69/EEC Method B3 and OECD Guideline No. 402
Deviations:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Type of coverage:
semiocclusive
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Table 7.2.2/1: Number of animals dead and number with evident toxicity

Dose
(mg/kg bw)

Conc.
in vehicle

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity(#/total)

Male

Female

Combined

Male

Female

Combined

2000

500 mg/ml

0

0

0

0

0

0

0

Mean erythema score for all animals:

at 24 hours: 0.7

at 48 hours: 0.4

at 72 hours: 0.2

Mean oedema score for all animals:

at 24 hours: 0.7

at 48 hours: 0

at 72 hours: 0

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study complete and sufficient to fulfill the endpoint requirements.

Additional information

Oral route:

In an acute oral toxicity study performed according to OECD 423 guideline and in compliance with Good Laboratory Practices, groups of 3 rats/sex were administered a single dose of 2000 mg/kg bw of the test substance by gavage.

Examinations for mortality, clinical signs and body weight gain were performed during the 14-day observation period. All surviving animals were necropsied at the end of the observation period. No mortality and no clinical signs were observed throughout the study. Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.

The acute oral combined LD50 was found greater than 2000 mg/kg b.w (McRae, 2000a).

Dermal route:

In an acute dermal toxicity performed according to OECD 402 guideline and in compliance with Good Laboratory Practices, the test substance formulated in 1%w/v aqueous methylcellulose was applied to the skin of five males and five females rats at a dosage of 2000 mg/kg bw.The application site was covered by a semi-occlusive dressing for 24 hours.

Examinations for mortality, clinical signs and body weight gain were performed during the 14-day observation period.

On completion of the observation period, the animals were sacrificed and then submitted to a macroscopic post-mortem examination.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. Body weight was not affected by the treatment.

Slight irritation was notable in seven rats following removal of the dressings on Day 2. In the majority of instances, the skin irritation resolved by Day 4 except in two animals where slight irritation persisted up to Day 5 or Day 10. In two animals,localized response (spots/scabbing) was first notable from Day 5 and persisted up to the study termination on Day 15 for one animal.

At necropsy, there were no macroscopic findings related to the test item administration.

The acute dermal LD50 was found greater than 2000 mg/kg bw (McRae, 2000b).

Inhalation:

In an acute inhalation toxicity performed according to OECD 403 guideline and in compliance with Good Laboratory Practice, one treated and one control group, each of five male and five female Sprague-Dawley rats were exposed by nose-only inhalation to the test substance for 4 hours at a concentration of 4.06 mg/l or air respectively. The concentration of 4.06 mg/l was the maximal practical atmosphere concentration.

Each animal was observed for mortality and clinical signs at hourly intervals during exposure, then one hour and two hours after exposure and at least twice a day during the 14-day observation period. Bodyweights were recorded before treatment then on day of exposure and weekly during the observation period. All surviving animals were necropsied at the end of the observation period.

No mortality occurred during the study. Clinical signs as exaggerated breathing was evident for all treated animals from 30 minutes during the exposure and immediatly post exposure, persisting for most animals to day 4. Gasping and noisy breathing were noted for some animals post-exposure, the latter sign persisting in 1 male to Day 4. The mean bodyweight gain for treated rats was less than controls during the first week following exposure. Thereafter, the mean bodyweight gain of female and male treated rats was similar to and less than control values respectively. There were no treatment-related findings at the macroscopic examination.

The 4 -hour inhalation LC50 was found to be greater than 4.06 mg/l (ie 4060 mg/m3) (Paul, 2000).


Justification for classification or non-classification

No mortalities were noted in rats either after treatment by oral or dermal routes with a single dose of 2000 mg/kg body weight or exposure by inhalation for 4 hours to 4.06 mg/L which was the maximum practicable concentration.

On the basis of these results and according to regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures, no classification is warranted with respect to acute oral, dermal and inhalation toxicity.