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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1998-06-24 to 1999-01-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study performed under GLP without deviations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
from 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
described in EC-Guideline 92/69
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Diguanidinium carbonate
EC Number:
209-813-7
EC Name:
Diguanidinium carbonate
Cas Number:
593-85-1
Molecular formula:
CH5N3.1/2CH2O3 (one guanidine species, as denoted in the ESIS database) CH5N3.CH5N3.CH2O3 (as in the crystalline from, basis for the molecular weight 180.1658 g/mol as given below)
IUPAC Name:
bis[amino(imino)methanaminium] carbonate
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Guanidine Carbonate Pure
- Substance type: Salt with organic kation and inorganic anion
- Physical state: White crystalline powder
- Analytical purity: 99.7 %
- Impurities: Sulphate ash <0.05 %, heavy metals calculated as lead, <10 ppm (mg/L), iron 1 ppm, lead <1 ppm, arsenic <3 ppm
- Purity test date: 1998-06-09
- Lot/batch No.: 1867 of Agrolinz Melamin GmbH, St.-Peter-Strasse 25, A-4021 Linz
- Expiration date of the lot/batch: Not specified but considered stable under conditions of storage for at least 5 years
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
other: Sprague Dawley, Him:OFA, SPF.
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Forschungsinstitut für Versuchstierzucht, A-2325 Himberg, Germany
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females)
- Weight at study initiation: 252-282 g (male), 225 - 251 g (female)
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm x 15 cm). Wire mesh lids. Sanitization of cages once a week. Bedding material: Aspen wood chips, type "4 HV" (Finn Tapvei Oy, SF-73620 Kortteinen), autoclaved. Bedding material was changed weekly.
- Diet (e.g. ad libitum): Altromin 1314 forte, gamma irradiated with 25 kGy 60Co, ad libitum (Producer: Altromin GmbH, D-32791 Lage).
- Water (e.g. ad libitum): Tap water, offered in Makrolon bottles with stainless steel canules, ad libitum.
- Acclimation period: 5 respectively 6 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (average)
- Humidity (%): 55 (average)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
The patch was soaked with deionised water to get optimal contact with the skin.
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal thoracal region, 5 x 6 cm, labelled in a relaxed animal (corresponding to an area of about 50 cm2, when the skin is slightly stretched at administration)
- % coverage: about 10 % of the estimated body surface
- Type of wrap if used: dressing (Fixomull Stretch, Fa. Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: no
Duration of exposure:
24 hours
Doses:
Range-finding study: 400, 894 and 2000 mg/kg bw
Main test: 2000 mg/kg bw
No. of animals per sex per dose:
Range-finding study:
400 mg/kg bw: 1 male, 1 female
894 mg/kg bw: 1 male, 1 female
2000 mg/kg bw: 1 male 1 female

Main test:
2000 mg/kg bw: 4 males, 4 females
Both animals dosed with 2000 mg/kg in the preliminary test were included into the main study, leading to 5 males and 5 females treated with 2000 mg/kg in the main test.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weight: before administration, 7 and 14 days after administration
Clinical observations: at least once per day.
Necropsy: 14 days after administration
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight

Results and discussion

Preliminary study:
In a range finding study three groups of one male and one female each were dosed with 400, 894 or 2000 mg per kg body weight. All animals survived for 14 days after administration. Therefore it was decided to perform a limit-test with one dose of 2000 mg per kg body weight. Both animals,
dosed with 2000 mg/kg in the preliminary test, were included into the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
3/5 males and 3/5 females were affected: The finding, observed earliest immediately after administration and latest 6 h after administration, was:
Chromodacryorrhoea on the day of the test substance administration was attributed to the discomfort, caused by the dressing which restricts the freedom of movement.
Body weight:
Males and Females: Body weight and body weight gain were inconspicuous during the whole study in all males. A slight body weight loss in the first week was noted in one female. Another female gained only 1 g body weight in the second week.
Gross pathology:
All animals in the main study were normal at terminal necropsy.
Other findings:
Sex differences: Effects on body weights were more pronounced in the females, who are considered therefore to be slightly more susceptible then the males.

Any other information on results incl. tables

Observations in life

A grade of severity was recorded where applicable (low - medium - high).

Findings

Dose (mg/kg), sex

No. of the affected animals

Observation time (after administration)

 

First / last

Maximum grade of severity

No findings at any time

2000, m

22, 25

- /-

-

 

2000, f

27, 28

- /-

-

Chromodacryorrhoea

 

2000, m

21

0.5 h / 6 h

low

23

1 h / 2 h

low

24

1 h / 6 h

low

2000, f

26

0.5 h / 2 h

low

29

2 h / 2 h

low

30

0.5 h / 1 h

low

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50, dermal of Guanidine carbonate is higher than 2000 mg/kg body weight in rats.
Executive summary:

A valid GLP-study was performed to investigate acute toxic effects of the test substance after a single dermal administration to rats. Methods and investigations were performed in conformance with OECD TG 402, 1987.

Guanidine carbonate was administered once dermally under semiocclusive conditions on an area of approximately 5 x 6 cm on the dorsal thoracal region of 5 male and 5 female Him:OFA rats (Sprague Dawley). The duration of the exposure was 24 hours. The dose was 2000 mg per kg body weight.

Body weight was measured before administration, 7 and 14 days after administration. Clinical observations were made at least once per day. Necropsy was performed 14 days after administration.

All animals survived until the scheduled termination of the study. Body weight and body weight gain were inconspicuous during the whole study in all males. A slight body weight loss in the first week was noted in one female. Another female gained only 1 g body weight in the second week. 3/5 males and 3/5 females were affected by chromodacryorrhoea on the day of application, lasting until maximum 6 h after administration. This effect was attributed to the discomfort caused by the dressing. The same signs were observed in both sexes. All animals were normal at the post mortem examination. Effects on body weights were more pronounced in the females, who are considered therefore to be slightly more susceptible than the males.

Except that the body weight gain of the females was slightly reduced, no toxic effects of the test substance were noted in life at the dose of 2000 mg/kg body weight. No mortality occurred. The LD50 of Guanidine carbonate is higher than 2000 mg/kg body weight in rats of either sex.

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