Reaction mass of trientine and trientine, mono- and di-propoxylated

Endpoint summary

Description of key information

Acute oral and dermal studies on the test material showed LD50 values of 4500 mg/kg bw for acute oral toxicity, and of > 2150 mg/kg for acute dermal toxicity in rats.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-guideline and pre-GLP Study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: TIF: RAC/F

Sex:

male/female

Details on test animals or test system and environmental conditions:

The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5 in a room kept at a constant temperature of 22 Î. 1°C and a relative humidity of approximately 50%. They were given water and food (NAFAG, Gossau SG, rat food) ad libitum. The rats were starved duringone night before starting the treatment.

Route of administration:

oral: unspecified

Vehicle:

polyethylene glycol

Details on oral exposure:

The test material was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 20, 30 and 40% with polyethylene glycol (PEG 400).

Doses:

2150, 3170 and 4640 mg/kg

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

not specified

Details on study design:

The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5 in a room kept at a constant temperature of 22 Î. 1°C and a relative humidity of approximately 50%. They were given water and food (NAFAG, Gossau SG, rat food) ad libitum. The rats were starved duringone night before starting the treatment.

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 500 mg/kg bw

Based on:

test mat.

Mortality:

At the end of the study on Day 7 there was a dose dependent trend evident with 0, 30 and 50% mortality at 2150, 3170 and 4640 mg/kg respectively

Gross pathology:

Congested liver was observed in animals that died during the study. No substance related gross organ changes were seen in aniamals that survived until the end of the test.

Other findings:

Within 2 to 3 hours of treatment the animals in all dosage groups showed dyspnoea, lachrymation, apathy, ruffled fur and curved position.
The surviving animals had recovered within 3 to 5 days. They were killed and autopsied after an observation period of 7 days.

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The acute oral LD 50 in rats of both sexes was observed over a period of 7 days. The LD50 was approximately 4500 mg/kg, the test material has therefore a slight acute toxicity to rats by this route of administration

Executive summary:

The test material was assessed for toxicity in an acute oral toxicity study with male and female rats. The test material was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 20, 30 and 40% with polyethylene glycol (PEG 400) and administered to the shaved back of each rat at doses of 2150, 3170 and 4640 mg/kg. Animals were observed 1, 24, 48 hours and 7 days following administration, within 2 to 3 hours of treatment the animals in all dosage groups showed dyspnoea, lachrymation, apathy, ruffled fur and curved position. The surviving animals had recovered within 3 to 5 days. They were humanely killed and autopsied after an observation period of 7 days.

The acute oral LD 50 of TK 10406 in rats of both sexes was observed over a period of 7 days the LD50 was approximately 4500 mg/kg, the compound has therefore a slight acute toxicity to rats by this route of administration.

According to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, there is no requirement for classification of the test material within the EU. Based on the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Second edition, 2007, the test material should be classified as Category 5 for acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 500 mg/kg bw

Quality of whole database:

The study is considered to be Klimisch code 2

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-guideline and pre-GLP Study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Noakes, D.N. and Sanderson, D.M. A method for determining the dermal toxicity of pesticides. Brit. J. Industr. Med., 26, 59-64, 1969

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif:RAI/F

Sex:

male/female

Details on test animals or test system and environmental conditions:

During treatment and for the 7 day observation period the rats were housed singly in Macrolon cages (Type 3) in a room kept at a constant temperature of 22± 1°C and a relative humidity of approximately 50%. They were given water and food (NAFAG, Gossau. SG, rat food) ad libitum. The animals were bred in-house, they were 7 to 8 weeks old and weighed 180 to 200 g.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 6 hours before treatment the rats'backs were shaved with an electric razor. The suspension was evenly dispersed on the skin with a
Record syringe and covered with aluminium foil, which was held around the trunk with ISO-ELAST plaster. After 24 hours the plaster and the
aluminium foil were peeled off carefully and the skin was cleaned with warm water to remove all traces of the suspension. The rats were the observedfor a 7-day period and symptoms recorded.

Duration of exposure:

24 hours

Doses:

2150 mg/kg (for technical reasons higher doses were not possibel)

No. of animals per sex per dose:

The compound was tested on 6 Tif.: RAI/f rats (3 male and 3 female), bred under SPF conditions They were 7 to 8 weeks old and weighed 180
200 g.

Control animals:

not specified

Details on study design:

Shaved backs of Rats were treated with an even dispersion of a weighed concentrate (2150 mg/kg) of the test material and covered with aluminium foil for a period of 24 hours. After 24-hours the aluminium foil was removed and the treatment site was cleaned with warm water to remove all traces of the suspension. The rats were obseved for 7-days and symptoms recorded.

Statistics:

Not applicable

Preliminary study:

No details

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 150 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities were observed

Clinical signs:

other: No symptoms and no local skin irritation were observed. The rats were killed and autopsied after an observation period of 7 days.

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

Not applicable

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The acute dermal LD50 of the test material in rats of both sexes observed over a period of 7-days was >2150 mg/kg

Executive summary:

The acute dermal toxicity (LD50) in rats of both sexes was tested and observed over a period of 7-days. The shaved backs of Rats were treated with an even dispersion of a weighed concentrate (2150 mg/kg) of the test material and covered with aluminium foil for a period of 24 hours. After 24-hours the aluminium foil was removed and the treatment site was cleaned with warm water to remove all traces of the suspension. The rats were obseved for 7-days and symptoms recorded.

During the test no mortality, no symptoms and no local skin irritation were observed during the 7 -day observation period. No substance related gross organ changes were seen during autopsy.

The acute dermal LD50 of the test material in rats of both sexes observed over a period of 7-days was >2150 mg/kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 150 mg/kg bw

Quality of whole database:

The study is considered to be Klimisch code 2

Additional information

Acute oral toxicity

The test material was assessed for toxicity in an acute oral toxicity study with male and female rats. The test material was weighed, suspended at 20, 30 and 40% with polyethylene glycol (PEG 400) and administered to the shaved back of each rat at doses of 2150, 3170 and 4640 mg/kg. Animals were observed 1, 24, 48 hours and 7 days following administration, within 2 to 3 hours of treatment the animals in all dosage groups showed dyspnoea, lachrymation, apathy, ruffled fur and curved position. The surviving animals had recovered within 3 to 5 days. They were humanely killed and autopsied after an observation period of 7 days.

The acute oral LD 50 in rats of both sexes was observed over a period of 7 days, the LD50 was approximately 4500 mg/kg, the test material has therefore a slight acute toxicity to rats by this route of administration.

Acute dermal toxicity

The acute dermal toxicity (LD50) in rats of both sexes was tested and observed over a period of 7-days. The shaved backs of Rats were treated with an even dispersion of a weighed concentrate (2150 mg/kg) of the test material and covered with aluminium foil for a period of 24 hours. After 24-hours the aluminium foil was removed and the treatment site was cleaned with warm water to remove all traces of the suspension. The rats were obseved for 7-days and symptoms recorded.

During the test no mortality, no symptoms and no local skin irritation were observed during the 7 -day observation period. No substance related gross organ changes were seen during autopsy.

The acute dermal LD50 of the test material in rats of both sexes observed over a period of 7-days was >2150 mg/kg

Justification for selection of acute toxicity – oral endpoint
One study available, although a pre-guidline study is available and considered sufficient to make conclusions

Justification for selection of acute toxicity – dermal endpoint
One study available, although a pre-guidline study is available and considered sufficient to make conclusions

Justification for classification or non-classification

Acute oral toxicity

According to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, there is no requirement for classification of the test material within the EU.

Acute dermal toxicity

The test material does not have to be classified for acute dermal toxicity in accordance with either EU Regulation (EC) No 1272/2008 or UN-GHS (2007).