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Description of key information

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-10 wks (males), 12-14 wks (females)
- Weight at study initiation: 235-247 g (males), 215-238 wks (females)
- Housing: individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot 261111)
- Diet (ad libitum): Altromin 1324 (lot 0715)
- Water (ad libitum): tap water, sulphur acidified to a pH of approximately 2.8
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: 10% of the total body surface
- Type of wrap if used: The test item was held in contact with the skin by a dressing throughout a 24-h period. The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: at the end of the 24 h exposure period the residual test item was removed using aqua ad injectionem

- For solids, paste formed: yes, the test substance was moistened with aqua ad injectionem
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: cageside observations were done several times on the days of dosing and once a day until the end of the observation period. Observations included general symptoms, changes in the skin and fur, eyes, and mucous membranes. Also changes in respiratory, circulatory, autonomic and centrals nervous system and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors convulsions, salivation, diarrhea, lethargy, sleep and coma. Weighing was done on day 1 (prior to application) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: primary skin irritation was assessed using the scoring system of Draize
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
A slight weight loss was recorded for 3 out of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. The male animals showed weight gain during the first and second week of the observation.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which was due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.
Other findings:
- Other observations: Erythema grade 1 was observed in 1 of 5 female animals on Days 2 and 3 after start of the application. Scratches and eschar were observed in all male and female animals. All signs of irritation were reversible within the observation period. Edema was not observed (see Tables 2 and 3).

Table 1: Body weight development (in g and %)

Sex

Day 1 (g)

Day 8 (g)

Day 15 (g)

Day 1-15 (%)

male

238

260

300

26

male

243

257

287

18

male

247

266

303

23

male

238

256

280

18

male

235

244

279

19

female

238

239

255

7

female

215

220

227

6

female

220

216

229

4

female

217

215

235

8

female

226

223

230

2

Table 2: Skin irritation: Individual data - Males

Day after start application

Animal No. 21

Animal No. 22

Animal No. 23

Animal No. 24

Animal No. 25

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

Day 2

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 3

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s*

Day 4

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

Day 5

0/0

es, s

0/0

es, s

0/0

es, s

0/0

(es, s)*

0/0

es, s

Day 6

0/0

es, s

0/0

es, s

0/0

es, s

0/0

(es, s)*

0/0

es, s

Day 7

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

Day 8

0/0

es, s

0/0

es, s

0/0

es, s

0/0

nsf

0/0

nsf

Day 9

0/0

es, s

0/0

es, s

0/0

es, s

0/0

nsf

0/0

nsf

Day 10

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 11

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 12

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 13

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 14

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 15

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Comments:

E = erythema, O = oedema; 1, 2, 3, 4 = scoring system laid down in OECD Guideline 404 (Table 2, Draize scoring system)

es = eschar, s = scratches, s* = small scratches, (es, s)* = eschar and scratches on the edge of the application site; nsf = no specific finding

Table 3: Skin irritation: Individual data - Females

Day after start application

Animal No. 26

Animal No. 27

Animal No. 28

Animal No. 29

Animal No. 30

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

Day 2

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 3

1/0

es, s*

0/0

es, s

0/0

es, s*

0/0

es, s*

0/0

s*

Day 4

1/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

0/0

nsf

Day 5

0/0

es, s

0/0

es, s

0/0

es, s

0/0

(es, s)*

0/0

nsf

Day 6

0/0

es, s

0/0

es, s

0/0

es, s

0/0

(es, s)*

0/0

nsf

Day 7

0/0

es, s

0/0

es, s

0/0

es, s

0/0

es, s

0/0

nsf

Day 8

0/0

nsf

0/0

es, s

0/0

es, s

0/0

nsf

0/0

nsf

Day 9

0/0

nsf

0/0

es, s

0/0

es, s

0/0

nsf

0/0

nsf

Day 10

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 11

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 12

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 13

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 14

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Day 15

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Comments:

E = erythema, O = oedema; 1, 2, 3, 4 = scoring system laid down in OECD Guideline 404 (Table 2, Draize scoring system)

es = eschar, s = scratches, s* = small scratches, (es, s)* = eschar and scratches on the edge of the application site; nsf = no specific finding

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
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

Dermal

According to OECD 402, 2000 mg/kg bw of silicon orthophosphate was dermally applied to the intact skin of 5 male and 5 female rats each (BSL, 2012). The test substance was placed on a wet gauze patch and applied to the skin for 24 h under occlusive conditions. After the exposure period, the gauze patch was removed and the treated skin was rinsed with water. There were no deaths or signs of toxicity during the study. A slight weight loss was recorded for 3 out of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. The male animals showed weight gain during the first and second week of the observation. With the exception of acute injection of blood vessels in the abdominal region, which was due to the euthanasia injection, no specific gross pathological changes were recorded for any animal. Erythema grade 1 was observed in 1 of 5 female animals 48 and 72 h after patch removal. This effect was fully reversible within 120 h after application of the test substance. Edema was not observed. Scratches and eschar were observed in all male and female animals from day 3 to day 9 at the latest. Hence, all signs of irritation were reversible within the observation period of 14 days. The LD50 of the test substance was > 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
No study required since exposure of humans via inhalation is unlikely taking into the lack of exposure into consideration: Silicon orthophosphate is only imported as already included as extrudate into the matrix of a catalyst. The substance is therefore inert and inhalation can be excluded. Therfore and due to animal welfare, acute oral toxicity was not tested.

Justification for selection of acute toxicity – inhalation endpoint
No study required since exposure of humans via inhalation is unlikely taking into the lack of exposure into consideration: Silicon orthophosphate is only imported as already included as extrudate into the matrix of a catalyst. The substance is therefore inert and inhalation can be excluded. Therfore and due to animal welfare, acute inhalation toxicity was not tested.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

The available data on dermal acute toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

No data on acute oral and inhalation toxicity are available.