Registration Dossier

Administrative data

Description of key information

no adverse effects in acute dermal study with dose levels up to and including 2000 mg/kg bw
No mortallity and only passing lethargy in an acute oral study with dose levels up to and including 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: Limit test, predating OECD protocols and GLP. Yet study outcome sufficient for decision on classification
Qualifier:
according to
Guideline:
other: IRLG (1981)
Deviations:
no
Principles of method if other than guideline:
range-finding study in the rat. 250, 500, 2500 and 5000 mg/kg bw on 2 males and 2 females per group, oral, gavage.
in the absence of any mortality, 5000 mg/kg bw on 5 male, 5 female animals
GLP compliance:
no
Test type:
other: Limit test "avant la lettre"
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton laboratories
- Age at study initiation: not given
- Weight at study initiation: 190-210 gr (males; 185-195 gr (females)
- Fasting period before study: overnight
- Housing: caged singly in Makrolon cages
- Diet (e.g. ad libitum): at lib
- Water (e.g. ad libitum): at lib
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: September To: October (dates not specified)
Route of administration:
oral: gavage
Vehicle:
water
Doses:
range-finding: 250, 500, 2500 and 5000mg/kg bw . Limit test: 5000 mg/kg bw
No. of animals per sex per dose:
range finding: 2/2, final study 5/5
Control animals:
no
Statistics:
not applicable
Preliminary study:
range-finding study in the rat. 250, 500, 2500 and 5000 mg/kg bw on 2 males and 2 females per group, oral, gavage.
No mortality, no clinical effects
Sex:
male
Dose descriptor:
LD0
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
lethargy from 30 minutes to one and and a half hour after dosing in 2 males and 2 females
Body weight:
Mormal increase during recovery period (see table)
Gross pathology:
none
Other findings:
none

body weights during recovery

Dose

(mg/kg)

animal nr Nr. , gender

Tag-1

Tag1

Tag8

Tag 1 5

5000

1, m

225

200

280

350

 

2, m

210

190

260

300

 

3,m

225

210

290

345

/

 

4,m

220

' 205

275

325

 

5, m

210

190

275

310 -

 

6 ,f

200

1 85

215

225

7,f

210

190

225

240

 

8,f

205

'1 95

280

330

 

9,f

190

1 85

230

260

-

10, f

205

1 95

2 30

230

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
non toxic
Executive summary:

Based on the results of the range-finding study, 10 sprague=dawley rats (5m, 5f) were given 5000 mg/kg bw, suspended in water by gavag of sodium mehtally sulphonate.

in 4/10 animals, a brief period of lethargy shorty after dosing was observed

Since all animals survived the 14 -day recovery period, the LD0 can be set at =5000 mg/kg bw.

No gross pathology was observed at obduction


Endpoint conclusion
Endpoint conclusion:
no 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
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:vCharles River Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: males 288 gr , females 190 gr (average)

ENVIRONMENTAL CONDITIONS
Animal husbandry
Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40
to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any
variations to these conditions were maintained in the raw data and had no effect on the outcome of the
study.
Accommodation
Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized 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).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During
the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18
cm).
Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
Water
Free access to tap water.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed
according to facility standard procedures.
There were no findings that could interfere with the study.

IN-LIFE DATES: From: To:
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Method Dermal application.
Clipping One day before exposure (Day -1) an area of approximately 5x7 cm on
the back of the animal was clipped.
Application The 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
formulation was held in contact with the skin with a dressing, consisting of
a surgical gauze patch (Surgy 1D)*, successively covered with aluminum
foil and Coban elastic bandage*. A piece of Micropore tape* was
additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul,
Minnesota, U.S.A. (Coban & Micropore).
Frequency Single dosage, on Day 1.
Dose level (volume) 2000 mg/kg (10 mL/kg) body weight.
Application period 24 hours, after which dressings were removed and the skin cleaned of
residual test substance using tap water.
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 / 5
Control animals:
not required
Details on study design:
Observations
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. The time of onset, degree and duration were
recorded and the symptoms graded according to fixed scales:
Final Report
Sodium methallylsulphonate Project 500480
- Page 10 -
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy At the end of the observation period, all animals were sacrificed by
oxygen/carbon dioxide procedure and subjected to necropsy.
Descriptions of all internal macroscopic abnormalities were recorded.
Sex:
male
Dose descriptor:
LD0
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Chromodacryorrhoea was noted in two males and two females on Day 1.
Scales were seen in the treated skin-area of two males and one female between Days 3 and 7.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats
used in this type of study and were therefore considered not indicative of toxicity
Gross pathology:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
sodium methallylsulfonate, tested in an acute dermal toxicity test, was found to have an LD0 of >= 2000 mg/kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

no adverse effects in acute dermal study wth dose levels up to and including 2000 mg/kg bw; no classification needed

No mortallity and only passing lethargy in an acute oral study with dose levels up to and including 5000 mg/kg bw ; no classification needed