Aluminium trititanium dodecachloride

Endpoint summary

Description of key information

Two acute toxicity studies by oral route are available. One was tested using dispersion in olive oil and found no adverse effect at 300mg/kg. Another test was carried out using hydrochloric acid solution of titanium trichloride.

The toxicity of the hydrochloride solution was said to be due to the corrosive effect of the test solution. So, LD50 by oral toxicity using rats was more than 300mg/kg.

With regard to aluminum chloride, three values are reported, 370, 1100 and 3700 mg/kg-bw.

Using additivity formula, oral acute toxicity LD50 of aluminum trititianium dodecachloride was estimated over 300 mg/kg-bw.

As for acute dermal toxicity of the test sample was conducted using hydrochloric aquoeus solution, no mortality was observed at 2000 mg/kg, but serious skin corrosion was observed.

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

Study period:

2003-12-18 to 2004-02-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

December 17, 2001

Deviations:

not specified

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:Tosoh FInechem Corp., Lot No,;THP1031
- concentration: 0.3 and 0.5 wt% in olive olil.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:Stable under inert atmosphere.
- Stability under test conditions:Not known
- Solubility and stability of the test substance in the solvent/vehicle:Not known

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles river Japan
- Females (if applicable) nulliparous and non-pregnant: [yes/no] Yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 211 g (207,1 - 218.6 g)
- Fasting period before study: Overnight
- Housing:Stainless steel net floor cages (260W x 300D x 150H mm)
- Diet (e.g. ad libitum): ad libitumm
- Water (e.g. ad libitum):ad libitu
- Acclimation period:9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2004-01-06 To:2004-01-29

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5 and 3.0%
- Amount of vehicle (if gavage):10 mL/kg
- Justification for choice of vehicle:good dispesion property
- Lot/batch no. (if required):
- Purity:

Doses:

50 mg/kg, 300 mg/kg

No. of animals per sex per dose:

Female 5 per gruop

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observation; 10 min, 30min, 1h, 2h, 3h and 4 h on administration day. Twice on the next day. after that observation was conducted once a day until 14th day after administration.
Weighing: 1,7,14 day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

not used

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Mortality:

Both groups (50 mg/kg and 300 mg/kg) did not show death after single oral treatment during whole (14 days post-treatment period) experiment. (Tabel 1)

Clinical signs:

10 minutes after administration of substance, all animals in 300 mg/kg showed decreased spontaneous locomotion and three of them showed decreased respiratory rate and incomplete eyelid opening. These symptoms became to disapear after 3 hours and completely disappeared after one day. In addition, one animal in 50 mg/kg group showed mucous stool.
This mucous stool was transient change after administration. As this symptom was sometimes observed by administration of olive oil, this observation was seemed to be due to administration of medium (olive oil).

Body weight:

all animals showed expected gains in body weight.

Gross pathology:

No abnormalities were observed at necropsy.

Table 1 Acute oral toxicity study in rats

Mortality

Sex	Exp group (mg/kg)	Number of deaths on day																						Mortality
		0								1	2	3	4	5	6	7	8	9	10	11	12	13	14(day)
		0^a)	5	10	30 (min)	1	2	3	4(h)
Female	50	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/5^b)
	300	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/5^b)

a)   Immediately after administration

b)   Number of dead animals/Number of animals

 

Table 2 Acute oral toxicity study in rats

Summary of clinical signs

Signs	Female
	50	300	mg/kg
	ta	ta
	5^a)	5
No abnormalities detected	4
Decreased spontaneouslocmotion		5
Decreased respiratory rate		3
Incomplete eyelid opening		3
Mucous stool	1

ta, terminal autopsy

a)   Number of animals examined

 

 

Table 3 Acute oral toxicity study in rats

Summary of body weights (g)

Sex	Exp. Group (mg/kg)	Number of animals	Observation period
			0	1	7	14	(day)
Female	50	5	188.4	210.4	230.5	247.5
			±2.3	±3.5	±13.5	±17.5
	300	5	192.7	207.6	231.6	254.1
			±4.6	±5.4	±4.2	±10.9

     Mean ± S.D.

 

Table 4 Acute oral toxicity study in rats

Summary of macroscopic examination

Findings	Female
	50	300	(mg/kg)
	ta	ta
	5^a)	5
No abnormalities detected	5	5

  ta, terminal autopsy.

   a) Number of animals examined.

Interpretation of results:

study cannot be used for classification

Conclusions:

The acute oral median lethal dose (LD50) of the substance in the female rat was estimated to be greater than 300 mg/kg bodyweight.

Executive summary:

The acute oral median lethal dose (LD50) of the substance in the female rat was estimated to be greater than 300 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Quality of whole database:

The data have been accumulated according to a clearly defined test methods but not in compliance with GLP.

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:

supporting study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

This study was carried out by Japanese government to confirm its toxicity.

Qualifier:

no guideline available

Version / remarks:

The study was carried out refer to OECD guideline, but guideline number was not specified.

Principles of method if other than guideline:

Similar to OECD 434

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Titanium trichloride is unstable substance and gradually decomposes at room temperature. Thus, the solution prepared by dissolving titanium in the hydrochloric acid solution was used as test material.
This solution was dark violet liquid and its density was 1.28 g/ml. the concentration was over 20%.

Species:

rat

Strain:

Wistar

Remarks:

Slc

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan SLC
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 week
- Weight at study initiation: Not known
- Fasting period before study:
- Housing:Metal cage (w 220 x D 220 x H170 mm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±1
- Humidity (%): 55 ± 5
- Air changes (per hr): 18
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hours light

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the body
- % coverage: approximately 10%
- Type of wrap if used: The test solution was spread on the lint cloth and be hold on the dorsal skin. The cloth was covered with aluminum foil and fixed with Tegaderm transparent dressing tape(Sumitomo 3M). In addition that, the trunk of the animal was swathed with Reston self-adhering foam pads (Sumitomo 3M) and Silkytex adhesive bandage.

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):2000 mg/kg as 20% titanium trichloride solution.
- Concentration (if solution): 20, 50 and 100 %
- Constant volume or concentration used: yes; constant concentration
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): not known.
- Concentration (if solution):25, 50 and 100%
- Lot/batch no. (if required): not available
- Purity:not known

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 rats per sex and dose.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:not known
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

not used

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

as 20 % solution

Mortality:

No

Clinical signs:

No abnormal signs were observed during exposure period.

Body weight:

Not known

Gross pathology:

Necropsy of all animals on 14th day was carried out. MIcroscopic examination of organs did not show any change.

Other findings:

Observation of skin after removal of the lint cloth, which contained test chemical.
The skin of contact area was seriously corroded and the skin was adhered on the lint cloth and bled for both male and female animals.
After 2nd day, the corroded skin turned to black and began eschar formation. After 5th day, the eschar began to desquamate from the edge of the eschar, but did not disappear even on the 14th day.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity study on titanium trichloride was conducted using 20% hydrochloric acid solution of titanium trichloride.
This solution showed serious skin corrosion, but no mortality was observed even in the dosage 2000 mg/kg. Thus LD50 was estimated over 2000mg/kg as 20 % solution.

Executive summary:

The acute dermal toxicity study on titanium trichloride was conducted using 20% hydrochloric acid solution of titanium trichloride. This solution showed serious skin corrosion, but no mortality was observed even in the dosage 2000 mg/kg. Thus LD50 was estimated over 2000mg/kg as 20 % solution.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Though serious skin corrosion was observed, but no mortality was observed at the maximum dose, 2000 mg/kg.The data have been accumulated according to a clearly defined test methods but not in compliance with GLP.

Justification for classification or non-classification

Acute Oral toxicity

No mortality was observed upto 300mg/kg using olive oil dispersion of titanium trichloride.

As for aluminum chloride, its LD50s were reported as 370, 1100 and 37000 mg/kg. According to additivity formula LD50 of aluminum trititanium dodecachloride was estimated to be more than 300 mg/kg..

Acute Dermal Toxicity

No mortality was observed upto the maximum dose, but serious skin corrosion was observed using hydrochloric acid aqueous solution. LD50 > 2000mg/kg.