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Description of key information

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:
from January to February 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
- According to Annex 3c the lower dose (200 mg) should be applied first to the same sex that was treated with 2000 mg/kg
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: HAN: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Schering AG, Germany
- Mean weight at study initiation: 105-113 g (males) or 89-91 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- rel. Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidist. water
Doses:
2000 and 200 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
After 2000 mg/kg bw all animals died within 3 hours on day 1 of the test. No mortality was observed after adiministration of 200 mg/kg bw in both sexes.
Clinical signs:
The main clinical findings after administration of 2000 mg/kg were apathy, prone position, unconsciousness, disturbances in gait, total and spontaneous twitches and a bluish discolouration of all hairless parts of the body prior to death. All animals treated with 200 mg/kg were without clinical findings over the whole study period.
Body weight:
The body weight gain was within the normal range for rats of the age and strain.
Gross pathology:
Autopsy revealed reddening of the glandular mucosa of the stomach in only one animal which died after application of 2000 mg/kg and no compound-related or suspected compound-related findings in the two other animals which died or in the animals which were sacrificed at the end of the study.
Conclusions:
The acute oral toxicity of the test item was moderate with an LD50 value of > 300 < 500 mg/kg bw in rats according to ANNEX 3c of OECD TG 423 (1996). All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg
Executive summary:

The acute oral toxicity of the test item was moderate with an LD50 value of > 300 < 500 mg/kg bw in rats according to ANNEX 3c of OECD TG 423 (1996). All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected in all treated animals. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
200 mg/kg bw

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
Study period:
from January to February 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- 3 instead of 5 animals/sex used
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HAN: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Schering AG, Germany
- Mean weight at study initiation: 104-106 g (males) or 98-105 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- rel. Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Vehicle:
other: 900 mg NaCl ad 100 ml bidist. water
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All treated animals survived
Clinical signs:
no clinical findings
Body weight:
The body weight gain was within the normal range for rats of the age and strain.
Gross pathology:
Autopsy revealed no compound-related findings.
Executive summary:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 402 the dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute toxicity: oral

The acute oral toxicity of the test item was moderate with an LD50 value of > 300 < 500 mg/kg bw in rats according to ANNEX 3c of OECD TG 423 (1996). All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected in all treated animals. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg bw.

Acute toxicity: dermal

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 402 the dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.


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

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

Justification for classification or non-classification

Acute toxicity: oral

LD50: > 300 - < 500 mg/kg bw (rat, female/male)

According to EU-Directive 67/548/EEC, Annex VI Triamin-Dihydrochlorid shall be classified as harmful (R22)

According to Regulation (EC) No 1272/2008, Annex I Triamin-Dihydrochlorid shall be allocated to Category 4 (H302)

Acute toxicity: inhalation

No data available

Acute toxicity: dermal

LD50: > 2000 mg/kg bw (rat, female/male)

No classification required according to EU-Directive 67/548/EEC, Annex VI

No classification required according to Regulation (EC) No 1272/2008, Annex I