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Description of key information

The LD(50) rat oral is > 5000 mg/kg bw
The LD(50) rat dermal is > 5000 mg/kg bw

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: simillar to guideline
Principles of method if other than guideline:
10 male Wistar rats/ group received single doses of the test item by gavage and were observed for clinical signs and mortality for 14 days
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 180-200 g
- Housing: 5 per cage
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
10 male Wistar rats/ group received single doses of aminoguanidinium hydrogen carbonate by gavage and were observed for clinical signs and mortality for 14 days.
Doses:
3100, 5000 mg/kg bw
No. of animals per sex per dose:
10 males/group
Control animals:
no
Details on study design:
10 male Wistar rats/ group received single doses of aminoguanidinium hydrogen carbonate by gavage and were observed for clinical signs and mortality for 14 days.
Statistics:
no data
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: In the 5000 mg group 4/10 animals died: sedation and poor general condition
Mortality:
No animal died in the 3100 mg/kg bw group.
4/10 animals died within 2 to 6 days in the 5000 mg/kg bw group.
Clinical signs:
other: 3100 mg/kg bw animals tolerated treatment without impairment 5000 mg/kg bw 10 /10: sedation, poor general condition
Gross pathology:
no details given
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Executive summary:

Groups of 10 male Wistar rats received single oral doses (3100 or 5000 mg/kg bw) of aminoguanidinium hydrogen carbonate dissolved in water and were observed for 14 days. Rats dosed with 3100 mg/kg bw tolerated the treatment without clinical signs or mortality. All 10 rats dosed with 5000 mg/kg bw showed sedation and poor general condition within 2 to 6 days after application of aminoguanidinium hydrogen carbonate, 4/10 died. Thus the LD50(oral) is >5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 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:
January 21, 2014 - February 5, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD guidelines and GLP so therefore meets the criteria of Klimisch code 1.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
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
- Strain: Crl:WI(Han)
- Age at study initiation: males: 8 weeks, females:12 weeks
- Weight at study initiation: All animals were within 20% of the mean weight
- Housing: Rats were held individually in Makolon cages, type III
- Diet (e.g. ad libitum): Free access to VRF1 (P); SDS Special Diet Services
- Water (e.g. ad libitum): Water Free access to tap-water.
- Acclimation period: At least 5 days prior to start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 % relative
- Air changes (per hr): approximately 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hour light / 12 hour dark cycle

IN-LIFE DATES: From: 21 January 2014 To: 5 February 2014
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Fur was clipped 24 hours before administration. The application area was 40 cm2.
Duration of exposure:
24 hours. The application site was covered with a semi-occlusive dressing. After removal of the dressing, the application site was washed with warm water.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: On day of dosing and day 7 and 14 following dosing.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs observed each day
Statistics:
No mortality occurred. Use of statistics not indicated
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: No mortality during study.
Mortality:
Mortality did not occur in treated animals.
Clinical signs:
other: No systemic clinical signs were observed during clinical observation.
Gross pathology:
No macroscopic abnormalities were noted in the animals examined on the last day of observation

Table 2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

 

Dose
(mg/kg bw)

Conc.
in vehicle (%)*

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

5000

 0/5

 0/5

0/10 

 

 0/5

 0/5

0/10
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortality has occurred at doses of 5000 mg/kg bw. The study has therefore been completed as a limit test, and the LD50 is considered to be more than 5000mg/kg.
Executive summary:

In an acute dermal toxicity study, groups of Winstar rats (5/sex) were dermally exposed to a single dose of 5000 mg/kg bw of Aminoguanidinium hydrogen carbonate which was covered by a semi-occlusive dressing for 24 hours. The animals were then observed for 14 days.

No mortality occurred and there were no systemic clinical signs of toxicity observed during clinical examination. Therefore the LD50 is considered to be > 5000 mg/kg.

This acute study is classified as reliable without restriction. It satisfies the guideline requirement for an acute dermal study in the rabbit.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Groups of 10 male Wistar rats received single oral doses (3100 or 5000 mg/kg bw) of aminoguanidinium hydrogen carbonate dissolved in water and were observed for 14 days. Rats dosed with 3100 mg/kg bw tolerated the treatment without clinical signs or mortality. All 10 rats dosed with 5000 mg/kg bw showed sedation and poor general condition within 2 to 6 days after application of aminoguanidinium hydrogen carbonate, 4/10 died. Thus the LD50(oral) >5000 mg/kg bw.

In an acute dermal toxicity study, groups of Winstar rats (5/sex) were dermally exposed to a single dose of 5000 mg/kg bw of Aminoguanidinium hydrogen carbonate which was covered by a semi-occlusive dressing for 24 hours. The animals were then observed for 14 days.

No mortality occurred and there were no systemic clinical signs of toxicity observed during clinical examination. Therefore the LD50 is considered to be > 5000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Reliable study according to scientifically accepted method.

Justification for selection of acute toxicity – inhalation endpoint
The substance is a solid, so it is unlikely that significant exposure will occur via inhalation. Therefore, this endpoint was waived.

Justification for selection of acute toxicity – dermal endpoint
Klimisch 1 study

Justification for classification or non-classification

According to the available data there is no reason for classification or labelling.