4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

minor deviation from recommended humidity.

GLP compliance:

yes

Test type:

other: Preliminary study, limit test and standard acute study (main study).

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

EC Number:

240-212-2

EC Name:

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Cas Number:

16068-37-4

Molecular formula:

C14H34O6Si2

IUPAC Name:

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no details
- Age at study initiation: no details
- Weight at study initiation g: male: 242-3 (pre-study); 250 (limit test); 265-283 (main test). female 220-223 (pre-study); 215 (limit test); 234-246 (main test).
- Fasting period before study: no details
- Housing: 1/cage; polycarbonate
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no details
- Humidity (%): no details except that humidity reached 73% (30-70% is recommended in the guideline)
- Air changes (per hr): no details
- Photoperiod (hrs dark / hrs light): no details

IN-LIFE DATES: no details

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: no details
- % coverage: 10%
- Type of wrap if used: no details

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no details
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): given in table 1
- Concentration: neat
- Constant volume or concentration used: no

Duration of exposure:

24h

Doses:

0, 1591, 1785, 2008, 2241, 2512 mg/kg bw

No. of animals per sex per dose:

5 in limit and main study, 2 in preliminary study.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation daily, weighed on days 0, 7, 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

Bliss method. Litchfield and Wilcoxon method.

Results and discussion

Preliminary study:

See table 1.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 972 mg/kg bw

95% CL:

1 850 - 2 101

Remarks on result:

other: Bliss method

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 977 mg/kg bw

95% CL:

1 734 - 2 255

Remarks on result:

other: Litchfield & Wilcoxon method

Mortality:

Mortality occurred from day 6-13 with higher susceptibility in the females.

Clinical signs:

other: Subdued behaviour and prostration from day 8-10. One case of abdominal distension was noted from day 9-12.

Gross pathology:

The majority of animals which died during the study showed haemorrhagic ascites, cloudy pleural liquid and thickening of the hepatic capsule. Thickening of the hepatic capsule was noted in treated animals euthanised on study termination. No macroscopically detectable abnormality was noted in control group.

Other findings:

Some cases of paleness of the cutaneous surface were noted from day 6 to day 14.

Any other information on results incl. tables

Table 1: Number of animals dead and with evident toxicity

Dose (mg/kg bw)	Volume ml/kg bw (neat)	Mortality (dead/total)			Time range of deaths (days)	Number with overt toxicity (no./total)	Description of toxicity/body weight/necropsy findings
		Male	Female	Combined		Combined male/female	Combined male/female
Control^c	purified water	0/5	0/5	0/10	-	0/10	No findings.
1009^a	1.04	0/2	0/2	0/4	to day 8	-	-
2008^a	2.07	0/2	0/2	0/4	to day 8	-	-
2008^b	2.07	0/5	5/5	5/10	days 8-13	5/10	Transient: prostration (3/10); subdued behaviour (2/10); abdominal distension (1/10). Females that died had haemorrhagic ascites (excess fluid containing blood in the peritoneal cavity, commonly associated with liver damage), thickening of the hepatic capsule (the membrane surrounding the liver), and pale lungs or cloudy pleural fluid, No macroscopic abnormalities were detected in males.
1591^c	1.64	0/5	0/5	0/10	-	1/10	Transient pale skin surface (1/10). Liver effects (thickening of hepatic capsule or granulomatous liver) (4/5f).
1785^c	1.84	0/5	4/5	4/10	days 8-11	4/10	Transient: pale skin surface (3/10); subdued behaviour (3/10). Significantly reduced body weight gains in both sexes. Possible liver effects (haemorrhagic ascites, discoloured liver, thickening of hepatic capsule) (5/5f, 5/5m). Lung (cloudy pleural fluid) (4/5f).
2008^c	2.07	0/5	3/5	3/10	days 7-13	3/10	Transient: pale skin surface (3/10); subdued behaviour (3/10); abdominal distension (1/10). Significantly reduced body weight gains in both sexes. Possible liver effects (haemorrhagic ascites, white or discoloured liver, thickening of hepatic capsule) (5/5f, 2/5m). Lung (cloudy pleural fluid) (3/5f, 1/5m).
2241^c	2.31	4/5	5/5	9/10	days 6-12	9/10	Transient: pale skin surface (5/10); subdued behaviour (7/10); abdominal distension (3/10). Significantly reduced body weight gains in both sexes. Possible liver effects (haemorrhagic ascites, thickening of hepatic capsule) (5/5f, 5/5m). Lung (cloudy pleural fluid) (5/5f, 3/5m).
2512^c	2.59	5/5	5/5	10/10	days 7-13	10/10	Transient: pale skin surface (5/10); subdued behaviour (7/10); abdominal distension (3/10); prostration (1/10). Not possible to ascertain body weight effects due to excessive mortality. Possible liver effects (haemorrhagic ascites, white liver, thickening of hepatic capsule) (5/5m, 3/5f). Lung (cloudy pleural fluid) (4/5f, 4/5m). Kidney (enlarged or darkened) (1/5m). Intestine (blackish) (1/5f).

a preliminary study

b fixed dose study

c main study

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

A reliable study conducted in compliance with the standard guideline and in accordance with GLP, identified an LD50 of 1972 mg/kg bw, with some evidence of toxicity from the lowest dose tested in the main study, of 1591 mg/kg bw.