Monalazone disodium

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 October 2018 - 3 December 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

Monalazone disodium

EC Number:

262-810-2

EC Name:

Monalazone disodium

Cas Number:

61477-95-0

Molecular formula:

C7H4ClNO4S.2Na

IUPAC Name:

disodium 4-[(chloroazanidyl)sulfonyl]benzoate

Test material form:

solid

Specific details on test material used for the study:

Test Item Name : Monalazone Disodium

CAS No. : Proprietary
Molecular Formula : C7H4ClNNa2O4S
Molecular Weight : 279.602 g/mol
Purity as per COA : >99% excluding water

Physical Appearance : White or Off white powder or crystals
Aqueous pH : 8-10
Lot No. : 72617S
Manufactured Date : 26-07-2017
Expiry date : 01-02-2019
Recommended Storage : Ambient (+18 to +36oC)
Photosensitive : Yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Invivo Biosciences, Shed No. 23, Katha No.3169, Assessment No. 154, Kodigehalli Village, Magadi Road, Bangalore-560091, Karnataka, India
- Females (if applicable) nulliparous and non-pregnant
- Age at study initiation: 8 to 9 Weeks
- Weight at study initiation: 208.5 to 216.0 g
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing:Rats were housed individually in standard polysulfone cages (Size: approximately L 425 x B 266 x H 185 mm), with stainless steel top grill having facilities for pelleted food and drinking water in polycarbonate bottle. Additionally, polycarbonate rat huts were placed inside the cage as an enrichment object and were changed along with the cage once a week. Bedding: steam sterilized
- Diet: Ad libitum. Hypro Rat & Mice pellet feed, manufactured by Krishna Valley Agrotech LLP, MIDC Kupwad block, Sangli, Maharashtra, was provided to animals.
- Water: Ad libitum. Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd, Mumbai 400001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes.
- Acclimation period: After physical examination for good health and suitability for experiment, the rats were acclimatized for eight to fourteen days before treatment for dose range finding and main study respectively under standard laboratory conditions. Animals were observed once daily during acclimatization period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25°C
- Humidity (%): 64 to 68%
- Air changes (per hr): 14.1 air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Administration / exposure

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 8 x 5 cm
- % coverage: 10% of body surface
- Type of wrap if used: adhesive tape wound around the torso

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the applied area was washed with deionized water and wiped dry using clean towel
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
Group and Dose tested (mg/kg) Study Rat Number Sex Bodyweight(g) Quantity Applied(mg)
G1 200 DRF Rw1981 F 209.0 42
G2 1000 DRF Rw1982 F 208.5 209
G3 2000 DRF Rw1983 F 210.3 421
G3 2000 §Main Rw1984 F 212.9 426
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): Based on the individual body weight, the test item at the doses of 200, 1000 & 2000 mg/kg body weight was weighed on an aluminium foil and made into a paste by adding sufficient volume (about 0.1 to 0.5 mL) of the Milli-Q water

Duration of exposure:

24 hours

Doses:

Study Group Dose(mg/kg body weight) No. ofRats Sex Rat numbers
DRF G1 200 1 F Rw1981
DRF G2 1000 1 F Rw1982
DRF G3 2000 1 F Rw1983
Main G3 2000 2 F Rw1984 and Rw1985
DRF: Dose Range Finding F: Female

No. of animals per sex per dose:

1 in DRF; 2 in main study

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs and pre-terminal deaths (mortality) once during first 30 minutes after application, and at hourly intervals for 6 hours after application on the day of treatment (day 1) and once daily during Days 2 to 15. In addition, the site of applied area was observed for skin reactions at 24, 48 and 72 hours after removal of test chemical using the Draize criteria. Body weights were recorded at Day 1, 8 and 15.
- Necropsy of survivors performed: yes. Microscopic examination was not carried out as no gross pathological changes were observed.
- Other examinations performed: clinical signs, body weight,organ weights, macroscopic examination

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No pre-terminal deaths (mortality) observed during the study.

Clinical signs:

other: There were no clinical signs observed during the study.

Gross pathology:

No abnormality was detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present study results, the acute dermal LD50 of Monalazone Disodium is more than 2000 mg/kg body weight in female Wistar rats.

Executive summary:

The objective of this acute dermal toxicity study was to assess the toxicological profile of the test item on application as a single semi-occlusive dermal application to rats. Groups of animals, of a single sex, were exposed to the test chemical in a stepwise procedure using the appropriate fixed doses. A range-finding study was conducted with a single animal at the doses of 200, 1000 and 2000 mg/kg body weight. The initial dose level was selected at the concentration expected to produce clear signs of toxicity without causing severe toxic effects or mortality. Further, the main study was conducted with two additional animals at the dose of 2000 mg/kg body weight. There were no clinical signs and pre-terminal deaths (mortality) observed during the study. There were no skin reactions at the site of application at 24, 48 and 72 hours after test patch removal (as per draize method).