Sodium 3-mercaptopropanesulphonate

Endpoint summary

Description of key information

1. Acute oral toxicity (1987), GLP, OECD 401, rats, gavage, 2500 mg/kg, 3180 mg/kg, 4000 mg/kg, 5000 mg/kg, LD50 3720 mg/kg bw (14 day survival), 4110 mg/kg bw (24 hour survival). 
2. Acute dermal toxicity (1987), GLP, OECD 402, rats, semiocclusive, 2.5 g/kg, 5.0 g/kg, 7.5 g/kg, LD50 > 7.5 g/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: GLP-study with minor deficiencies in the report details

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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

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.

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:

other: 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.

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 720 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)

Rationale for reliability incl. deficiencies:

other: GLP-study with minor deficiencies in the report details

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

other: "Appraisal for 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

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF-Wistar rats (breeding Winkelmann, Paderborn, Germany)
- Weight at study initiation: ca. 210 g
- Housing: animals were kept in groups of 5 males and 5 females (divided at random) in individual cages
- Diet (e.g. ad libitum): laboratory standard diet (Altromin, Lage)
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ° C ± 2 ° C
- Humidity (%): 50 - 60%
- Photoperiod (hrs dark / hrs light): daily lighting for 12 hours.

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

the product was diluted 1 to 1 with water, prior to application

Details on dermal exposure:

For reasons of optimal application of the substance and to allow good skin contact, the animals were shaved completely on the back. The entire trunk was wrapped with two layers of gauze and the undiluted substance was applied to the shaved localization. The treated area was covered with a thin plastic shell and coated with Stülpa. To avoid slipping, the whole body was bonded with adhesive tape, avoiding simultaneously oral ingestion and dehydration of the 1: 1 in water applied substance. The animals were left for 24 hours in this manner. Then the animals were carefully "unpacked" and cleaned with a wet, very warm cloth. The completely wet animals were individually dried by a hairdryer and only after reaching the "optimal cleaned" state, were put in individual farming. After dermal administration, the animals were observed individually housed for 14 days, were they were evaluated using as criteria, the symptoms of poisoning, the clinical behaviour and mortality.

Duration of exposure:

24 h

Doses:

2.5, 5.0 and 7.5 g/kg bw

No. of animals per sex per dose:

5 males and females per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were conducted after 24 h, 48 h, after 7 and after 14 days, weighing was done at the beginning and the end of the study
- Necropsy of survivors performed: yes/no: yes (macroscopically examined for pathological changes)
- Other examinations performed: clinical signs, body weights

Statistics:

No data given on statistical methods

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7.5 other: g/kg bw

Based on:

test mat.

Remarks on result:

other: No animals died

Mortality:

No mortalities occurred.

Clinical signs:

other: The animals behaved after the application a little more quiet than normal, which can be attributed to the bandage. After unpacking and in the further following-up period, the animals behaved physiologically.

Gross pathology:

In the end section no macroscopic anatomical or pathological findings in the belly, chest and skull were noted.
At the treated spinal sites there were no deviations from normal findings. The dorsal skin appeared subjectively in the highest dose group a little dry or leathery.

Other findings:

no data

Table 1: weekly protocol for clinical observations - group 1

testing period: 7 / 14 days p.a., group:  I = 2,5 g/kg     animal-no.:1-10
Sex:  5 m + 5 f
examination (macroscopically)	summary of findings
Appearance/ behaviour	physiological
reflexes	physiological without special findings
fur and skin turgor	physiological, hair was growing evenly
orifices	physiological without special findings
faeces (colour and consistency)	physiological without special findings
body weight / food and water intake	normal body weight gain, normal food and water intake
acute symptoms	none

Table 2: weekly protocol for clinical observations - group 2

testing period: 7 / 14 days p.a., group:  II = 5,0 g/kg     animal-no.:1-10
Sex:  5 m + 5 f
examination (macroscopically)	summary of findings
Appearance/ behaviour	physiological
reflexes	physiological without special findings
fur and skin turgor	physiological, hair was growing evenly
orifices	physiological without special findings
faeces (colour and consistency)	physiological without special findings
body weight / food and water intake	normal body weight gain, normal food and water intake
acute symptoms	none

Table 3: weekly protocol for clinical observations - group 3

testing period: 7 / 14 days p.a., group: III = 7,5 g/kg     animal-no.:1-10
Sex:  5 m + 5 f
examination (macroscopically)	summary of findings
Appearance/ behaviour	physiological
reflexes	physiological without special findings
fur and skin turgor	physiological, hair was growing evenly
orifices	physiological without special findings
faeces (colour and consistency)	physiological without special findings
body weight / food and water intake	normal body weight gain, normal food and water intake
acute symptoms	none

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 402 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1).The validity criteria of the test system was fulfilled. The test material did not induce any signs of acute dermal toxicity. The test material was considered to be not toxic via the dermal exposure route under the conditions of the test, which is based on the LD50 values derived from this study (LD50 > 7.5 g/kg bw).

Executive summary:

The acute dermal toxicity of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (MPS) was investigated in rats (Dickhaus and Heisler, 1987). The substance was applied under semi-occlusive conditions to the skin for 24 h. No mortalities occurred and no clinical signs were reported. Therefore the test substance has an LD50 > 7.5 g/kg bw and can be regarded as non-toxic via the dermal exposure route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 500 mg/kg bw

Additional information

Acute oral toxicity:

The acute oral toxicity of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (MPS) was investigated in rats (Dickhaus and Heisler, 1987). 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. 5 male and 5 female rats per group received doses of 2500 mg/kg bw, 3180 mg/kg bw, 4000 mg/kg bw or 5000 mg/kg bw via a rigid tube orally. 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.

Acute dermal toxicity:

The acute dermal toxicity of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt (MPS) was investigated in rats (Dickhaus and Heisler,1987). The study was performed according to the OECD Guideline 402 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system were fulfilled. The substance was resuspended in water (1:1) and applied semi-occlusive to the skin for 24 h. No mortalities occurred and no clinical signs were reported. The test material did not induce any signs of acute dermal toxicity. The test material was considered to be not toxic via the dermal exposure route under the conditions of the test, which is based on the LD50 values derived from this study (LD50 > 7.5 g/kg bw).

Prediction using TOXTREE (v2.5.0)

The chemical structure of 1-Propanesulfonic acid, 3-mercapto-, monosodium salt was assessed by Toxtree (v.2.5.0) modelling tool for its toxicity class according to the rules of Cramer (with extensions). 1-Propanesulfonic acid, 3-mercapto-, monosodium salt is allocated in the “TOXTREE Toxicity Class Low”, which is characteristically for substances with a simple chemical structure with efficient modes of metabolism suggesting a low order of oral toxicity.

Justification for selection of acute toxicity – oral endpoint
best study available

Justification for selection of acute toxicity – dermal endpoint
best study available

Justification for classification or non-classification

Acute oral toxicity:

According to OECD guideline 401 the LD50 cut-off of the test substance is 2000 mg/kg bw. According to the European regulation (EC) No. 1272/2008 the test item should not be classified as toxic via the oral route, since the LD50 is 3720 mg/kg bw.

Acute dermal toxicity:

According to the European regulation (EC) No. 1272/2008 the test material does not meet the criteria for classification and will not require labelling for dermal toxicity.