Silicon orthophosphate

Endpoint summary

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:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

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.