Aminoguanidinium hydrogen carbonate

Endpoint summary

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.