Registration Dossier
Registration Dossier
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EC number: 254-447-3 | CAS number: 39430-51-8
Endpoint summary
Administrative data
Description of key information
LD50 (oral, rat) > 5000 mg/kg bw
LD50 (dermal, rat) > 2000 mg/kg bw
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 August - 20 August 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- and EU Method B.1 tris directive 2004/73/EC (Acute Oral Toxicity - Acute Toxic Class Method)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Groupe Interministeriel des Produits Chimiques
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Elevage JANVIER, Le Genest St Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 189 - 200 g
- Fasting period before study: food was removed one day prior to dosing
- Housing:by groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contained sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry
- Water (e.g. ad libitum): tap water from public distribution system
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 24
- Humidity (%): 42 - 67
- Air changes (per hr): at least ten changes
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg body weight - Doses:
- single dose of 2000 mg/kg body weight
- No. of animals per sex per dose:
- 6 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations, weighing at days 0, 2, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights - Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Mortality:
- No deaths occured.
- Clinical signs:
- other: No clinical signs observed.
- Gross pathology:
- No treatment related changes.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified
Reference
Table: Clinical observations (N = normal, No = none)
Observations: |
Females |
|||||
T0 + 30 min. T0 + 1 Hour T0 + 3 Hours T0 + 4 Hours |
Rf |
Rf |
Rf |
Rf |
Rf |
Rf |
1100 |
1101 |
1102 |
1106 |
1107 |
1108 |
|
Spontaneous activity |
N |
N |
N |
N |
N |
N |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
Convulsions |
No |
No |
No |
No |
No |
No |
Tremors |
No |
No |
No |
No |
No |
No |
Body temperature |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
Mortality |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||
Table: Clinical observations continued (N = normal, No = none)
Observations: |
Females |
|||||
D1 to D14 |
Rf |
Rf |
Rf |
Rf |
Rf |
Rf |
1100 |
1101 |
1102 |
1106 |
1107 |
1108 |
|
Spontaneous activity |
N |
N |
N |
N |
N |
N |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
Convulsions |
No |
No |
No |
No |
No |
No |
Tremors |
No |
No |
No |
No |
No |
No |
Body temperature |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
Mortality |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||
Table: Body weight and weight gain in grams
Females |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
Rf 1100 |
189 |
205 |
16 |
225 |
36 |
240 |
51 |
Rf 1101 |
193 |
215 |
22 |
236 |
43 |
264 |
71 |
Rf 1102 |
195 |
226 |
31 |
228 |
33 |
264 |
69 |
Rf 1106 |
190 |
213 |
23 |
213 |
41 |
241 |
51 |
Rf 1107 |
200 |
223 |
23 |
243 |
43 |
258 |
58 |
Rf 1108 |
198 |
217 |
19 |
231 |
33 |
253 |
55 |
Mean |
194.2 |
216.5 |
22.3 |
232.3 |
38.2 |
253.3 |
59.2 |
Standard deviation |
4.4 |
7.5 |
5.0 |
6.4 |
4.8 |
10.8 |
8.8 |
Table: necropsy data females Rf1100 - Rf1102 (X = Euthanasia, at term; N.t.r = nothing to report)
Observed organs |
Results |
|
Oesophagus |
X |
N.t.r. |
Stomach |
X |
N.t.r. |
Duodenum |
X |
N.t.r. |
Jejunum |
X |
N.t.r. |
Ileon |
X |
N.t.r. |
Caecum |
X |
N.t.r. |
Colon |
X |
N.t.r. |
Rectum |
X |
N.t.r. |
Spleen |
X |
N.t.r. |
Liver |
X |
N.t.r. |
Thymus |
X |
N.t.r. |
Trachea |
X |
N.t.r. |
Lungs |
X |
N.t.r. |
Heart |
X |
N.t.r. |
Kidneys |
X |
N.t.r. |
Urinary Bladder |
X |
N.t.r. |
Ovaries |
X |
N.t.r. |
Uterus |
X |
N.t.r. |
Treatment Area |
- |
- |
Adrenals |
X |
N.t.r. |
Pancreas |
X |
N.t.r. |
Particulars: none |
||
Table: necropsy data females Rf1106 - 1108 (X = Euthanasia, at term; N.t.r. = nothing to report)
Observed organs |
Results |
|
Oesophagus |
X |
N.t.r. |
Stomach |
X |
N.t.r. |
Duodenum |
X |
N.t.r. |
Jejunum |
X |
N.t.r. |
Ileon |
X |
N.t.r. |
Caecum |
X |
N.t.r. |
Colon |
X |
N.t.r. |
Rectum |
X |
N.t.r. |
Spleen |
X |
N.t.r. |
Liver |
X |
N.t.r. |
Thymus |
X |
N.t.r. |
Trachea |
X |
N.t.r. |
Lungs |
X |
N.t.r. |
Heart |
X |
N.t.r. |
Kidneys |
X |
N.t.r. |
Urinary Bladder |
X |
N.t.r. |
Ovaries |
X |
N.t.r. |
Uterus |
X |
N.t.r. |
Treatment Area |
- |
- |
Adrenals |
X |
N.t.r. |
Pancreas |
X |
N.t.r. |
Particulars: none |
||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Value:
- mg/kg bw
- Quality of whole database:
- The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 August - 19 August 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- and EU Method B.3 of the directive 92/69/EEC (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Groupe Interministeriel des Produits Chimiques
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Elevage JANVIER, Le Genest St Isle, France
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 223 - 237 g (males), 205 - 227 g (females)
- Fasting period before study: no
- Housing: during treatment in individual cage (solid-bottomed clear polycarbonate cages with stainless steel mesh lid; sawdust bedding, changed at least two times a week; conventional air condition); at D3 animals were put into cage by 2 or 3
- Water: tap-water from public distribution
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 48 -72
- Air changes (per hr): at least 10 changes
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: To: - Type of coverage:
- semiocclusive
- Vehicle:
- water
- Details on dermal exposure:
- TEST SITE
- Type of wrap if used: porous gauze dressing
REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with distilled water
- Time after start of exposure: 24 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw test item diluted in distilled water; effective dose of 2000 mg/kg bw
test item - Duration of exposure:
- 24 h
- 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: 14 days
- Frequency of observations and weighing: observations daily, weighing on day 0, 2, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Remarks on result:
- other: No deaths occured. No clinical signs.
- Sex:
- male/female
- Dose descriptor:
- other: local NOAEL
- Effect level:
- >= 11 other: mg/cm²
- Remarks on result:
- other: No local effects were observed.
- Mortality:
- none
- Clinical signs:
- other: none
- Gross pathology:
- no treatment related changes
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified
Reference
Table: clinical observations (N = normal, No = none)
Observations |
Males |
Females |
||||||||
T0 + 1 Hour T0 + 3 Hours T0 + 4 Hours |
Rm |
Rm |
Rm |
Rm |
Rm |
Rf |
Rf |
Rf |
Rf |
Rf |
1087 |
1088 |
1089 |
1090 |
1091 |
1092 |
1093 |
1094 |
1095 |
1096 |
|
Spontaneous activity |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Convulsions |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No |
Tremors |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No |
Body temperature |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Mortality |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
None |
None |
||||||||
Table: clinical observations (N = normal, No = none)
Observations |
Males |
Females |
||||||||
D1 to D14 |
Rm |
Rm |
Rm |
Rm |
Rm |
Rf |
Rf |
Rf |
Rf |
Rf |
1087 |
1088 |
1089 |
1090 |
1091 |
1092 |
1093 |
1094 |
1095 |
1096 |
|
Spontaneous activity |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Preyer’s reflex (noise) |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Respiratory rate |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Convulsions |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No |
Tremors |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No |
Body temperature |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Muscle tone |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Palpebral opening |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Pupil appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Salivation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Lachrymation |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Righting reflex |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Back hair appearance |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
Treatment site |
N* |
N* |
N* |
N* |
N* |
N* |
N* |
N* |
N* |
N* |
Mortality |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Remarks |
N* = slight green coloration at D1 and D2 |
|||||||||
Table: body weight and weight gain in grams
Males |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
Rm 1087 |
232 |
238 |
6 |
273 |
41 |
309 |
77 |
Rm 1088 |
230 |
237 |
7 |
276 |
46 |
323 |
93 |
Rm 1089 |
227 |
231 |
4 |
265 |
38 |
306 |
79 |
Rm 1090 |
237 |
245 |
8 |
282 |
45 |
324 |
87 |
Rm 1091 |
223 |
231 |
8 |
261 |
38 |
300 |
77 |
Mean |
229.8 |
236.4 |
6.6 |
271.4 |
41.6 |
312.4 |
82.6 |
Standard deviation |
5.3 |
5.8 |
1.7 |
8.4 |
3.8 |
10.6 |
7.1 |
Females |
D0 |
D2 |
D2-D0 |
D7 |
D7-D0 |
D14 |
D14-D0 |
Rf 1092 |
205 |
220 |
15 |
234 |
29 |
257 |
52 |
Rf 1093 |
208 |
213 |
5 |
224 |
16 |
254 |
46 |
Rf 1094 |
211 |
213 |
2 |
230 |
19 |
242 |
31 |
Rf 1095 |
206 |
212 |
6 |
226 |
20 |
250 |
44 |
Rf 1096 |
227 |
226 |
-1 |
242 |
15 |
255 |
28 |
Mean |
211.4 |
216.8 |
5.4 |
231.2 |
19.8 |
251.6 |
40.2 |
Standard deviation |
9.0 |
6.1 |
6.0 |
7.2 |
5.5 |
5.9 |
10.3 |
Table: necroscopic observations males (X = Euthanasia, at term; N.t.r. = nothing to report)
Observed organs |
Results |
|
Oesophagus |
X |
N.t.r. |
Stomach |
X |
N.t.r. |
Duodenum |
X |
N.t.r. |
Jejunum |
X |
N.t.r. |
Ileon |
X |
N.t.r. |
Caecum |
X |
N.t.r. |
Colon |
X |
N.t.r. |
Rectum |
X |
N.t.r. |
Spleen |
X |
N.t.r. |
Liver |
X |
N.t.r. |
Thymus |
X |
N.t.r. |
Trachea |
X |
N.t.r. |
Lungs |
X |
N.t.r. |
Heart |
X |
N.t.r. |
Kidneys |
X |
N.t.r. |
Urinary Bladder |
X |
N.t.r. |
Testicles |
X |
N.t.r. |
Ovaries |
- |
- |
Uterus |
- |
- |
Treatment Area (Skin) |
X |
N.t.r. |
Adrenals |
X |
N.t.r. |
Pancreas |
X |
N.t.r. |
Particulars: none |
||
Table: necroscopic observations females (X = Euthanasia, at term; N.t.r. = nothing to report)
Observed organs |
Results |
|
Oesophagus |
X |
N.t.r. |
Stomach |
X |
N.t.r. |
Duodenum |
X |
N.t.r. |
Jejunum |
X |
N.t.r. |
Ileon |
X |
N.t.r. |
Caecum |
X |
N.t.r. |
Colon |
X |
N.t.r. |
Rectum |
X |
N.t.r. |
Spleen |
X |
N.t.r. |
Liver |
X |
N.t.r. |
Thymus |
X |
N.t.r. |
Trachea |
X |
N.t.r. |
Lungs |
X |
N.t.r. |
Heart |
X |
N.t.r. |
Kidneys |
X |
N.t.r. |
Urinary Bladder |
X |
N.t.r. |
Testicles |
- |
- |
Ovaries |
X |
N.t.r. |
Uterus |
X |
N.t.r. |
Treatment Area (Skin) |
X |
N.t.r. |
Adrenals |
X |
N.t.r. |
Pancreas |
X |
N.t.r. |
Particulars: none |
||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.
Additional information
Acute oral toxicity
In the oral toxicity study performed by Seguier (2008) according to OECD 423 and GLP, 6 female Wistar rats were treated with 2000 mg/kg bw of the test substance in water by gavage. After application of the test substance and during the 14 day-observation period, no mortality occured, no clinical signs and no effects on the body weight gain were observed in any animal. Macroscopic examinations at necropsy did not reveal any abnormalities.
According to the acute toxic class method described in the OECD guideline 423, if there is no mortality following administration of 2000 mg/kg bw in two separate steps, the LD50 cut-off limit is 5000 mg/kg bw. Therefore, the LD50 is considered to be 5000 mg/kg bw for female rats.
Acute dermal toxicity
The acute dermal toxicity of the test substance was investigated in a study performed according to OECD 402 and GLP (Seguier, 2008). A single test substance dose of 2000 mg/kg bw was applied on the skin of five male and five female Sprague-Dawley rats. The treated skin site was covered with a semiocclusive dressing for 24 h. No mortality occurred during the 14 day-observation period. No clinical signs and no changes on body weight were observed and the necropsy revealed no test substance-related findings. Therefore, the LD50 is > 2000 mg/kg bw for male and female rats.
Justification for selection of acute toxicity – oral endpoint
There is only one study available.
Justification for classification or non-classification
The available data on the acute oral and dermal toxicity of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.
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