Carbazamidine sulphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, April 2011; including the most recent partial revisions.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Guanidinium phosphate (1:1)

EC Number:

226-551-9

EC Name:

Guanidinium phosphate (1:1)

Cas Number:

5423-22-3

Molecular formula:

CH5N3.H3O4P

IUPAC Name:

Guanidium phosphate (1:1)

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean: males 261-286g, females 185-215g
- Housing: Individually housed in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and elastic bandage. A piece of tape was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

VEHICLE water
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research and on test substance data supplied by the sponsor

Dose volume: 2000 mg/kg (10 mL/kg) body weight

DOSAGE PREPARATION: \\ tekst onder Preparation toevoegen

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: none.

Statistics:

None

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Piloerection was noted in five males and three females on Day 1. In addition, one male and one female showed chromodacryorrhoea on that day.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

Scales and/or macular erythema were seen in the treated skin-area of all five females during the observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw for guanidinium phosphate (1:1) was determined.

Executive summary:

An acute dermal toxicity study was performed with rats, according to OECD/EC test guidelines. Five male and five female rats were dermally exposed to guanidinium phosphate at 2000 mg/kg bw. No mortality occurred, and minor clinical symptoms were noted ( piloerection in five males and three females; one male and one female with chromodacryorrhoea, all on day 1 only). Scales and/or macular erythema were seen in the treated skin-area of all five females during the observation period. No unexpected changes in body weight gain occurred and no abnormalities were found at necropsy.

Based on these data, an LD50 >2000 mg/kg bw for guanidinium phosphate (1:1) was determined. Therefore, the substance is not classified for dermal toxicity according to Regulation (EC) No 1272/2008.