2-methyl-N-(4-sulfamoylphenyl) prop-2-enamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 - 19 Dec 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

adopted 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

438-940-2

EC Name:

-

Cas Number:

56992-87-1

Molecular formula:

C10 H12 N2 O3 S

IUPAC Name:

2-methyl-N-(4-sulfamoylphenyl) prop-2-enamide

Test material form:

other: powder aggregated into lumps

Details on test material:

- Name of test material (as cited in study report): SPM-N
- Physical state: white lumps with powder
- Lot/batch No.: T-9314
- Expiration date of the lot/batch: 29 Aug 2008
- Storage condition of test material: at room temperature in the dark
- Other: pH 7.6-7.5 (1% in water, indicative range)

Test animals

Species:

rat

Strain:

other: Wistar Crl:WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 263 ± 11 g (mean ± SD, males); 189 ± 5 g (mean ± SD, females)
- Housing: during the study period, animals were housed individually in labelled Macrolon cages (MII type; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom). During the acclimatisation period, animals were housed in groups in Macrolon type MIV cages.
- Diet: pelleted rodent diet SM R/M-Z (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0-21.7
- Humidity (%): 40-59
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 5 Dec 2007 To: 19 Dec 2007

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 25 cm² for males and 18 cm² for females
- % coverage: 10
- Type of wrap if used: the test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), covered with aluminium foil, which was covered with Coban elastic bandage. A piece of Micropore tape was additionally used to fix the wrapping in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated site was cleaned of residual test substance using tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 10 mL/kg bw
- Concentration: 200 mg/mL (w/w) (calculated from 10 mL/kg bw amount and 2000 mg/kg bw)
- Constant volume or concentration used: yes

VEHICLE
- Concentration (if solution): 10 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and morbidity twice daily; the occurrence of clinical signs was recorded at periodic intervals on Day 1 (0, 2, 4 h after administration) and once daily thereafter until Day 15; body weight was recorded on Day 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

Systemic effects were observed on Day 1 up to 4 h after administration. Flat posture was observed in 2/5 males 2 and 2-4 h after dosing on Day 1, respectively, while chromodacryorrhoea was noted in 4/5 males and 1/5 females 0, 2 or 4 h after administration (see Table 1 and 2).

Body weight:

The body weight gains were within the normal ranges in males and females during the whole study period.

Gross pathology:

No substance-related findings were noted at macroscopic post mortem examination of the animals..

Other findings:

- Other observations: Mild local effects on the treated skin were seen throughout the study period. White staining of the skin was noted in all animals for up to 4 consecutive days in the period Day 2-5. Scales or scabs were seen in 1/5 males and 3/5 females for 1-10 consecutive days in the period Day 4-15, while focal erythema was observed in 2/5 females on Day 3 or 3-4, respectively.

Any other information on results incl. tables

Table 1: Mortality and clinical signs

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
2000	0/5/5	0 h on Day 1 – Day 10	-	0
Females
2000	0/5/5	0 h on Day 1 – Day 15	-	0
Overall LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with systemic clinical signs         

 third number = number of animals used                               

 

Table 2: Overview of clinical signs and duration

Observations	Males (time of observation)					Females (time of observation)
No.	1	2	3	4	5	1	2	3	4	5
Systemic
Flat posture				2-4 h, Day 1	2 h, Day 1
Chromodacryorrhoea (snout)	0 h, Day 1	2 h, Day 1	4 h, Day 1	4 h, Day 1		4 h, Day 1
Treated skin
Scales grading slight (1) to severe (3)			Day 6-10 grade: 1							Day 12 grade: 1
White staining	Day 2-5	Day 2-4	Day 2-3	Day 2-3	Day 2	Day 2-4	Day 2-4	Day 2-4	Day 2	Day 2
Scabs grading slight (1) to severe (3)							Day 4-15 grade: 1	Day 5-14 grade: 1		Day 8-11 grade: 1
Focal erythema grading slight (1) to very severe (4)						Day 3 grade: 1				Day 3-4 grade: 1

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified