Registration Dossier

Administrative data

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: GLP-study with minor deficiencies in the report details

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", by the Staff of the Division of Pharmacology, FDA, 1959
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-Mercaptopropansulfonsaures Natrium (MPS)
- Name of test material: 1-Propanesulfonic acid, 3-mercapto-, monosodium salt
- Substance type: organic salt
- Physical state: white powder
- Lot/batch No.: 43 399
- Other: for the experiment, the substance was resuspended in CMC and administered by gavage to the rats.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SPF-Wistar rats (Breeder , Winkelmann, Paderborn, Germany )
- Weight at study initiation: ca 210 g
- Fasting period before study: 16 hours
- Housing: at random allocated to 4 groups, singly housed
- Diet (e.g. ad libitum): Laboratory standard diet (Altromin, Lage) ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature:22°C ± 2°C,
- Humidity (%): 50 - 60 %
- Photoperiod (hrs dark / hrs light): 12 hours light and dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
Details on oral exposure: the suspension was applied to the animals orally by a rigid tube.

VEHICLE
- Concentration in vehicle: 25 % or 30 %
- Amount of vehicle (if gavage): 1 ml per 100 g bw

MAXIMUM DOSE VOLUME APPLIED: 1.7 ml per 100 g bw
Doses:
2500 mg/kg bw (25% solution), 3180 mg/kg bw (30% solution), 4000 mg/kg bw (30% solution), 5000 mg/kg bw (30% solution)
The animals in group I and II were given 1.0 ml per 100 g body weight, the animals in group III 1.3 ml/100 ml in group IV 1.7 ml per 100 g bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
not specified
Details on study design:
After 16 hours of fasting the animals received the substance via a rigid tube orally.
Then the animals were observed (individually housed) for 14 days and were evaluated using as criteria, the symptoms of poisoning, the clinical behaviour and occurring mortality. On 14th Day post applicationem the animals were killed, dissected and examined macroscopically for pathological changes.
Statistics:
The LD50 oral was calculated according to Litchfield & Wilcoxon in combination with the Gauß's integral.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 110 mg/kg bw
Based on:
test mat.
95% CL:
3 740 - 4 520
Remarks on result:
other: for 24 hour survival
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 720 mg/kg bw
Based on:
test mat.
95% CL:
3 380 - 4 090
Remarks on result:
other: for 14 day survival
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: all animals survived
Sex:
male/female
Dose descriptor:
LD100
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: within 24 hours all animals died
Mortality:
No animals died in the 2500 mg/kg bw dose group.
In the 3180 mg/kg bw dose group one animal died within the first 7 days.
In the 4000 mg/kg bw dose group 3 animals died within 24 hours and another 3 within the following 6 days.
All animals in the 5000 mg/kg bw dose group died within 24 hours.
Clinical signs:
The results of intoxication were poisoning, characterized by ruffled hair coat, abdominal pain, proptosis, laboured respiration, tumbling and coordination disorders.
In the highest dose group, these symptoms increased in a few hours from sedation to coma. Mortalities were mostly seen within the first 24 hours.
Body weight:
Body weights also showed a clear indication of intolerance.
In the dose groups I and II all animals showed a decreased body weight gain compared with the standard. A dose-dependent trend was observed within the test groups.
Gross pathology:
In the section of the acute deceased rats and in the end section the gross pathological investigations did not reveal any treatment-related macroscopic anatomical and pathological findings within the thoracic cavity of the skull. Macroscopic inspection of the section showed in the acute mortality hyperaemia in the stomach and intestines.
The end section showed hyperaemia in the intestinal tract, very bright kidneys and a flushed bright pancreas.
Other findings:
no other findings reported

Any other information on results incl. tables

Clinical effects: In all dose groups mostly ruffled hair coat, abdominal pain syndrome, exophthalmos, cramps, staggering and incoordination were observed after the treatment.
The acute symptoms of sedation increased into coma. The animals usually died within 24 hours post application, more animals died 48 and 72 hours post application.

Table 1: Clinical findings - weekly report for group 1

weekly report for clinical findings
testing period:  7 & 14 days  p.a., group I = 2500 mg/kg, animal-no.:1-10
Sex:  5 males +5 females
examination (macroscopically) summary of findings
behaviour physiological, not special findings
reflexes jumpy
fur, skin turgor physiological, not special findings
orifices physiological, not special findings
faeces (colour, consistency) physiological, not special findings
Bodyweights, food and water intake decreased body weight gain, despite normal food and water intake
acute symptoms sedation, laboured breathing, abdominal pain
Table 2: Clinical findings - weekly report for group 2
weekly report for clinical findings
testing period:  7 & 14 days  p.a.,  group:  II = 3180 mg/kg, animal-no.:9
Sex:  5 males +4 females
examination (macroscopically) summary of findings
behaviour physiological, not special findings
reflexes decreased fur hygiene and jumpy behaviour
fur, skin turgor ruffled fur
orifices physiological, not special findings
faeces (colour, consistency) soft and smeary
Bodyweights, food and water intake decreased body weight gain, decreased food and water intake 
acute symptoms sedation, laboured breathing, Sedation, exophthalmia, abdominal pain,  coma and exitus letalis in one animal within the first 72 hours
Table 3: Clinical findings - weekly report for group 3
weekly report for clinical findings
testing period:  7 & 14 days  p.a.,  group: III = 4000 mg/kg, animal-no.:4
Sex: 2 males +2 females
examination (macroscopically) summary of findings
behaviour physiological, not special findings
reflexes decreased fur hygiene and jumpy
fur, skin turgor ruffled fur, clean impression
orifices physiological, not special findings
faeces (colour, consistency) moist
Bodyweights, food and water intake decreased body weight gain, decreased food and water intake 
acute symptoms 3 animals died within 24 hours and 3 died later with abdominal pain, cramps and coma within 72 hours after application
Table 4: Clinical findings - weekly report for all groups
weekly report for clinical findings
testing period:  7 & 14 days  p.a.  group: IV= 5000 mg/kg, animal-no.: 1 -10
Sex: 5 males +5females
examination (macroscopically) summary of findings
behaviour all animals died within 24 hours after application 
reflexes  
fur, skin turgor  
orifices  
faeces (colour, consistency)  
Bodyweights, food and water intake  
acute symptoms sedation (apathy and coma), exophthalmia and abdominal pain

Table 5: single findings of acute toxicity testing - group 1

single findings of acute toxicity testing of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (8CI, 9 CI)
Group I, Project-no. 1-4-95-87, Species: rat, application: oral, date: June 1987
No. sex dose    actual body weight

mortalities

body weight

symptoms

(mg/kg) dose at start 24 h 48 h 7 days at end (Irvin-screening)
1 m 2500 2.12 212       264 apathy, ataxia
2 m 2500 2.16 216       262 abdominal pain
3 m 2500 2.16 216       268  
4 m 2500 2.12 212       252 ruffled fur
5 m 2500 2.10 210       250  
6 f 2500 2.04 204       216  
7 f 2500 2.06 206       212  
8 f 2500 2.02 202       210  
9 f 2500 2.04 204       209  
10 f 2500 2.08 208       218  
solvent: CMC, concentration 25 %, conduction of test: H.

Table 6: single findings of acute toxicity testing - group 2

single findings of acute toxicity testing of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (8CI, 9 CI)
Group II, Project-no. 1-4-95-87, Species: rat, application: oral, date: June 1987
No. sex dose    actual body weight mortalities body weight symptoms
(mg/kg) dose at start 24 h 48 h 7 days at end (Irvin-screening)
1 m 3180 2.27 214       264 apathy, ataxia
2 m 3180 2.31 218       268 abdominal pain, cramps
3 m 3180 2.31 218       244 exophthalmos
4 m 3180 2.23 210       255 ruffled fur and coma
5 m 3180 2.26 213       250  
6 f 3180 2.14 202       214  
7 f 3180 2.16 204     + -  
8 f 3180 2.28 208       219  
9 f 3180 2.14 202       206  
10 f 3180 2.20 208       216  
solvent: CMC, concentration 30 %, conduction of test: H.

Table 7: single findings of acute toxicity testing - group 3

single findings of acute toxicity testing of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (8CI, 9 CI)
Group III, Project-no. 1-4-95-87, Species: rat, application: oral, date: June 1987
No. sex dose    actual body weight mortalities body weight symptoms
(mg/kg) dose at start 24 h 48 h 7 days at end (Irvin-screening)
1 m 4000 2.88 216       252 apathy, exophthalmos
2 m 4000 2.88 216 +     - ataxia and sedation
3 m 4000 2.91 218   +   - abdominal pain, and coma
4 m 4000 2.80 210     + - moribund
5 m 4000 2.80 210       240  
6 f 4000 2.72 204   +   -  
7 f 4000 2.72 204 +     -  
8 f 4000 2.75 206 +     -  
9 f 4000 2.75 206       204  
10 f 4000 2.77 208       216  
solvent: CMC, concentration 30 %, conduction of test: H.

Table 8: single findings of acute toxicity testing - group 4

single findings of acute toxicity testing of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (8CI, 9 CI)
Group IV, Project-no. 1-4-95-87, Species: rat, application: oral, date: June 1987
No. sex dose    actual body weight mortalities body weight symptoms
(mg/kg) dose at start 24 h 48 h 7 days at end (Irvin-screening)
1 m 5000 3.57 214 +     - apathy, sedation
2 m 5000 3.60 216 +     - abdominal pain, cramps, lacrimal secretion
3 m 5000 3.63 218 +     - moribund
4 m 5000 3.50 210 +     -  
5 m 5000 3.55 213 +     -  
6 f 5000 3.48 209 +     -  
7 f 5000 3.45 207 +     -  
8 f 5000 3.37 202 +     -  
9 f 5000 3.37 202 +     -  
10 f 5000 3.42 205 +     -  
solvent: CMC, concentration 25 %, conduction of test: H.

Table 9: observations (gross pathology) - group 1

organ animal no. Observations
CNS group I  - 10 animals anat.-pathol. without specific findings
lung " anat.-pathol. without specific findings
heart/pericard " anat.-pathol. without specific findings
stomach " slightly hyperaemic
small/large intestine " slightly hyperaemic
liver " anat.-pathol. without specific findings
spleen " anat.-pathol. without specific findings
kidney " paler than normal, a little grainy
serosa/vessels " flushed pancreas, despite that without specific findings
lymph nodes " anat.-pathol. without specific findings
gonadal glands " anat.-pathol. without specific findings

Table 10: observations (gross pathology) - group 2

organ animal no. Observations 
CNS group II  - 9 animals 1 animal died, anat.-pathol. without specific findings
lung " anat.-pathol. without specific findings
heart/pericard " anat.-pathol. without specific findings
stomach " anat.-pathol. without specific findings
small/large intestine " slightly hyperaemic
liver " anat.-pathol. without specific findings
spleen " anat.-pathol. without specific findings
kidney " paler than normal, a little grainy
serosa/vessels " flushed pancreas, despite that without specific findings
lymph nodes " anat.-pathol. without specific findings
gonadal glands " anat.-pathol. without specific findings

Table 11: observations (gross pathology) - group 3

organ animal no. Observations
CNS group III - 4 animals 6 animals died, anat.-pathol. without specific findings
lung " anat.-pathol. without specific findings
heart/pericard " anat.-pathol. without specific findings
stomach " anat.-pathol. without specific findings
small/large intestine " hyperaemic, but anat.-pathol. Without specific findings 
liver " anat.-pathol. without specific findings
spleen " anat.-pathol. without specific findings
kidney " paler than normal, a little grainy
serosa/vessels " flushed pancreas, despite that without specific findings
lymph nodes " anat.-pathol. without specific findings
gonadal glands " anat.-pathol. without specific findings

Table 12: observations (gross pathology) - group 4

organ animal no. Observations
CNS all acute mortalities (mean of all groups) anat.-pathol. without specific findings
lung " anat.-pathol. without specific findings
heart/pericard " anat.-pathol. without specific findings
stomach " stomach and GIT-mucosa highly flushed and significantly hyperaemic
small/large intestine " stomach and GIT-mucosa highly flushed and significantly hyperaemic
liver " anat.-pathol. without specific findings
spleen " anat.-pathol. without specific findings
kidney " anat.-pathol. without specific findings
serosa/vessels " anat.-pathol. without specific findings
lymph nodes " anat.-pathol. without specific findings
gonadal glands " anat.-pathol. without specific findings

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study was performed according to the OECD Guideline 401 without deviations and considered to be of high quality (reliability Klimisch 2). The validity criteria of the test system are fulfilled. The substance did not show a high toxicity after a single oral application to rats. The LD50 was identified to be 4110 mg/kg bw for the 24 h survival and 3720 mg/kg bw for the 14 day survival.
Executive summary:

The acute oral toxicity of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (MPS) was investigated in rats (Dickhaus and Heisler, 1987). The rats received doses of 2500 mg/kg bw, 3180 mg/kg bw, 4000 mg/kg bw or 5000 mg/kg bw via a rigid tube intragastrically. The main symptoms of intoxications were ruffled hair coat, abdominal pain, proptosis, laboured respiration, tumbling and coordination disorders. All animals in the highest dose group died within 24 hours. In the 4000 mg/kg bw dose group 3 animals died within 24 hours and another 3 within the following 6 days. In the 3180 mg/kg bw dose group one animal died within the first 7 days. No animals died in the lowest dose group. Therefore the oral toxicity can be characterised by a LD50 value of 4110 mg/kg bw for a 24 hour survival and a 3720 mg/kg bw for a 14 day survival.