Ammonium 2-mercaptopropionate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From July 10, 1990 to August 07, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: E.E.C.: Directive 84/449

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species, strain: Ico rat OFA.SD. (IOPS Caw),
Supplier: Iffa-Credo (69592 L'Arbresle Cedex - France),
Age: young adults between 5 and 7 weeks old.
Weight at the start of treatment (main study): from 117 g to 160 g (the individual weighs for each sex varied by no more than 20 % of the mean weight of the animals).

Environmental conditions:
Cages housed by sex and in groups of 5 (or 2 for the preliminary study), in type FI polycarbonate cages (interior dimensions 305 x 180 x 184 mm) for the preliminary study and in type MI (interior dimensions 365 x 225 x 180 mm) for the main study.
Air changes: at least 10 per hour
Temperature: 22 ± 3 °C
Humidity: 30 to 70 %
Lighting: artificial, 12 hours out of 24.
Hygiene: bedding changed once a week; cages changed for each study.
Diet: complete pelleted rat-mouse maintenance diet ad libitum (U.A.R., formula A.04 CR - U.A.R.).
Water: softened and filtered (0.6 µm) mains drinking water ad libitum. Bacteriological and chemical analyses checked twice a year.
Acclimatisation period: 8 days before the start of treatment.
Clinical examinations: at reception then before the start of treatment to ensure that only healthy animals are included in the study.
Identification of animals: perforation of ear pinna before the start of treatment.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Single oral administration by gestric gavage - round –ended curved stainless-steel oesophageal probe, 3 mm diameter, Perfektum.

Doses:

Preliminary test: 499, 998 and 2007 mg/kg
Main test: 1125, 1415, 1601 and 1786 mg/kg

No. of animals per sex per dose:

Preliminary study: 6 males, 6 non-pregnant females;
Main study:
control group - 5 males, 5 non-pregnant females;
groups 2 to 5 (treated) - 20 males, 20 non-pregnant females.

Control animals:

yes

Details on study design:

Preliminary test:
3 groups each composed of 2 males and 2 females were treated, at dose levels of 499, 998 and 2007 mg/kg respectively at a volume of 0.43, 0.86 and 1.73 ml/kg of test substance as supplied. The test substance was administered after about 18 h of a water regime and received food 4 h after intubation.

Main test:
Five groups of 5 females and 5 males were dosed with at the levels of 1125, 1415, 1601 and 1786 mg/kg, corresponding to 0.97, 1.22, 1.38 and 1.54 ml/kg respectively. The control group was treated with the distilled water under the same conditions. The test article was administered once only after about 17 h of a water regime and received food 4 h after intubation.

Following examinations were performed:
- Clinical examinations: 15 minutes after intubation, then at 1, 2 and 4 hours and then daily for 14 days.
The daily observations performed, amongst others, included changes in the skin and fur, the eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention.
- Observation of body weight: Day -1, Days 1 (before administration of the test article), 8 and 15, as well as at the time of death from Day 2 onwards.
- Necropsy examination of all animals. The abdominal and thoracic cavities were opened and particular attention was paid to the following organs: liver, heart, kidneys and lungs.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 518 mg/kg bw

Based on:

test mat.

95% CL:

> 1 435 - < 1 606

Mortality:

20 % in 1415 mg/kg dose level; 80 % in 1601 mg/kg dose level; 90 % in 1786 dose level.

Clinical signs:

other: At all tested doses: all animals showed subdued behaviour 15 min, 1, 2 and 4 h after administration of the test substance. At 1125 mg/kg: all surviving animals were normal on the day following treatment. At 1415 mg/kg: one rat showed tremors at 1 h. All

Gross pathology:

Animals which died during the study showed congested area in the lungs. No macroscopic determinable abnormality was noted in animals killed on study termination.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the study conditions, the LD50 of the test substance in the rat (male and female) was determined to be 1518 mg/kg bw (1435-1606) by the Bliss method and 1522 mg/kg bw (1421-1630) by the Litchfield & Wilcoxon’s method.

Executive summary:

A study was conducted to determine the potential toxic effect of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 401 and EC Directive 84/449. Five groups of 5 females and 5 males were dosed with the test substance at the levels of 1125, 1415, 1601 and 1786 mg/kg. The control group was treated with the distilled water under the same conditions. Mortality and abnormal clinical signs were noted 15 minutes after intubation, then at 1, 2 and 4 h, and then daily for the 14 d study period. All the animals were weighed the day before treatment (Day -1), immediately before administration of the test substance (Day 1), on Days 8 and 15, as well as at time of death from Day 2 onwards. A necropsy was performed for all the animals dead during the study and for all surviving rats after the 14 d study period and the final observation (Day 15). Under the study conditions, the LD50 of the test substance in the rat (male and female) was determined to be 1518 mg/kg bw (1435-1606) by the Bliss method and 1522 mg/kg bw (1421-1630) by the Litchfield & Wilcoxon’s method (Lheritier, 1990).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 01, 1999 to December 09, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

The density was determined at a temperature of 24 °C and used to calculate the appropriate dose volume for the required dose level.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley CD (Crl : CD® (SD) IGS BR) strain rats supplied by Charles River (UK) Ltd, Kent were used. At the start of the main study the males weighed 226 to 247 g, and the females 201 to 240 g, and were eight to twelve weeks old. After a minimum acclimatisation period of five days the animals were selected at given an unique number within the study by indelible ink-marking on the tail and a number written on a cage card.

The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, UK) was allowed throughout the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administrated to each animal was calculated according to its fasted body weight at the time of dosing.

No. of animals per sex per dose:

Preliminary test: 1
Main test: 5

Control animals:

not specified

Details on study design:

Preliminary study:

A range-finding study was performed to establish a dosing plan using one female and one male. The dose level was 2000 mg/kg bw (1.72 mL/kg bw; density: 1.166 g/mL).
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 h after dosing and subsequently once daily for five days. Individual body weights were recorded on the day of dosing to allow calculation of individual dose volumes. No necropsies were performed.

Main study:

Based on the results of the range-finding study three groups of 5 animals of the same sex were dosed at logarithmically spaced dose levels as follows: 1000 mg/kg bw (0.86 ml/kg bw), 1414 mg/kg bw (1.22 ml/kg bw), 2000 mg/kg bw (1.72 ml/kg bw).
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 h after dosing and subsequently once daily for up to fourteen days.
In order to establish that the untreated sex were not markedly more sensitive to the test substance, an additional group of five males was treated with highest dose of 2000 mg/kg bw.
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 h after dosing and subsequently once daily for five days. Individual body weights were recorded prior to dosing on Day 0 and on Days 7 and 14 or at death.
At the end of the study the surviving animals were killed by cervical dislocation. All animals, including those that died during the study, were subjected to gross pathological examination. This consisted of an external examination and examination of the major organs of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Data evaluations included the relationship between the animals exposed to the test substance and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, the acute oral median lethal dose (LD50) and 95 % confidence limits of the test material were calculated using a probit method of Finney DJ 'Probit Analysis' 1971, Cambridge University Press. The LD50 and 95 % confidence limits were calculated for females only.

Preliminary study:

Range-finding Study:
There were no deaths. Clinical signs of toxicity noted were ataxia, hunched posture and pilo-erection. Based on this information, dose levels of 1000, 1414 and 2000 mg/kg bw were selected for the main study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 797 mg/kg bw

Based on:

test mat.

95% CL:

> 1 262 - < 2 560

Mortality:

Deaths were noted during the day of dosing and one day after dosing. The slope of the probit curve is equal to 2.9958 probit units per log10 dose.

Clinical signs:

other: Clinical signs of toxicity noted in all dose groups were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration. Pilo­erection was also noted in animals treated with 1414 or 2000 mg/kg. Incidents of tonic and/or clonic conv

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

Male animals were considered not to be markedly more sensitive to the test substance than female animals.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the study conditions, the acute oral LD50 and 95 % confidence limits of the test substance were calculated to be 1797 (1262 - 2560) mg/kg bw.

Executive summary:

A study was conducted to determine the potential toxic effect of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 401 and EU Method B.1. Following a range-finding study, three groups of five fasted female animals were given a single oral dose of undiluted test substance at dose levels of 1000, 1414 and 2000 mg/kg bw. A further group of five fasted males was similarly treated, at a dose level of 2000 mg/kg bw. The surviving animals were observed for 14 d after the day of dosing. All animals were subjected to gross pathological examination. Deaths were noted during the day of dosing and one day after dosing. Clinical signs of toxicity noted were ataxia, clonic and tonic convulsions, hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, loss of righting reflex, increased salivation, occasional body tremors and splayed gait. Surviving animals recovered one to five days after dosing. Surviving animals showed expected gain in bodyweight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study. Under the study conditions, the acute oral LD50 and 95% confidence limits of the test substance were calculated to be 1797 (1262 - 2560) mg/kg bw (Sanders, 2000).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 518 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EEC directive 84/449/EEC

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Appearance: pink-coloured cream

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Strain: Crl.: (WI) BR - Wistar, white
Source: Firma Charles River Wiga, Sandhofer Weg 7, 8714 Sulzfeld
Animal identification: coloured marking; cage labelled with the following information: dosage, sex, date of study
Weight range at study initiation: m: 177 - 186 g, f: 168 - 201 g
Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type III)
Illumination: artificial lighting (120 lux) from 7. 00 a.m. - 7.00 p.m.
Temp.: 20 ± 2 °C
Relative humidity: 50- 85 %
Measurement: with thermohygrometer twice daily

Prior to study initiation, the animals were acclimated to laboratory conditions for at least 7 days. 24 h before treatment, the fur was removed with electric clippers from an area of roughly 5 x 10 cm on the back of each animal. The skin was subsequently examined for abrasions and animals with healthy, intact skin were then coloured for individual identification.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Preparation and application of the test substance:
The test substance was administered as a 66.6 % dilution at 3 ml/kg body weight. The pH value has been adjusted to 6.8 with 25 % ammonic solution. The relative density of the applied solution was 1.002 kg/l. For practical reasons the terms ml and g are considered as identical units.
A single dermal application of the test substance was performed. The substance was held in contact with the skin with a porous gauze dressing and Elastoplast (Beiersdorf).

Duration of exposure:

The exposure period was 24 h.

Doses:

66.6 % dilution at 3 ml/kg body weight

No. of animals per sex per dose:

f males and 5 females

Control animals:

not required

Details on study design:

Range finding
A preliminary range finding test with a dose of 2000 mg/kg bw was conducted on two female rats.

Main study
Clinical observations:
In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure (Screening Methods in Pharmacology, R. A. Turner, 1965, p. 26). Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the following intervals after patch removal: 10 min, 1 h, 2 h, 4 h, 24 h, and thereafter once daily up to day 14.

Skin reactions:
After patch removal, dermal irritation was evaluated once daily for 14 days according to a scheme based on Draize.

Body weights:
The body weights of all animals were recorded immediately before treatment (day 0) and surviving animals were reweighed on days 7 and 14 (termination).

Necropsy:
Animals found dead or killed in extremis were immediately necropsied. The surviving animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were subsequently performed.

Evaluation of the data:
LD50 values were calculated according to Finney D.Y., Probit Analysis, 3rd edition, Cambridge, 1971.

Preliminary study:

There were no deaths in the preliminary study.

Key result

Sex:

male/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 animals died during the course of the main study.

Clinical signs:

other: Some animals showed a slight to moderate reduced activity 10 min - 4 h p.a. Otherwise, no abnormal clinical signs were observed. A very slight till moderate erythema was observed in almost all of the animals for the entire observation period. Some animals

Gross pathology:

Gross pathological examinations at 14 days p. a. (terminal necropsies) revealed no test substance-dependent findings. Those macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which often occur spontaneously in rats of this strain and age.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the 14 d dermal LD50 was established at >2000 mg/kg bw in male and female rats.

Executive summary:

A study was conducted to determine dermal toxicity of the test substance (2-mercaptopropionic acid) according to OECD Guideline 402 and EC Directive 84/449. The acute dermal toxicity of the test substance was investigated in 5 male and 5 female Wistar rats. On the basis of the range finding results, each animal was given a single dermal administration of 2000 mg/kg bw as a 66.6% dilution. The pH was adjusted to 6.8 with a 25% ammonic solution. The skin was exposed to the test substance for 24 h and signs of erythema and oedema were subsequently evaluated once daily for 14 d. Clinical observations were conducted at regular intervals during the 14 d observation period. Body weights were measured on Days 0, 7 and 14. Gross pathological examinations were performed on animals at termination. No abnormal clinical signs were observed apart from a slight to moderate reduced activity in the animals. A very slight till well-defined erythema was observed in almost all of the animals for the entire observation period. Some animals had eschar on the skin and wrinkled skin 5 - 14 d post-administration (p.a.). No signs of oedema were observed. No pre-terminal deaths occurred. All animals showed normal weight gains. Gross pathological examinations at 14 d p.a. (terminal necropsy) revealed no test substance-dependent findings. Under the study conditions, the 14 d dermal LD50 was established at >2000 mg/kg bw in male and female rats (Kaufmann, 1990).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity oral

Study 1:

A study was conducted to determine the potential toxic effect of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 401 and EC Directive 84/449. Five groups of 5 females and 5 males were dosed with the test substance at the levels of 1125, 1415, 1601 and 1786 mg/kg. The control group was treated with the distilled water under the same conditions. Mortality and abnormal clinical signs were noted 15 minutes after intubation, then at 1, 2 and 4 h, and then daily for the 14 d study period. All the animals were weighed the day before treatment (Day -1), immediately before administration of the test substance (Day 1), on Days 8 and 15, as well as at time of death from Day 2 onwards. A necropsy was performed for all the animals dead during the study and for all surviving rats after the 14 d study period and the final observation (Day 15). Under the study conditions, the LD50 of the test substance in the rat (male and female) was determined to be 1518 mg/kg bw (1435-1606) by the Bliss method and 1522 mg/kg bw (1421-1630) by the Litchfield & Wilcoxon’s method (Lheritier, 1990).

Study 2:

A study was conducted to determine the potential toxic effect of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 401 and EU Method B.1. Following a range-finding study, three groups of five fasted female animals were given a single oral dose of undiluted test substance at dose levels of 1000, 1414 and 2000 mg/kg bw. A further group of five fasted males was similarly treated, at a dose level of 2000 mg/kg bw. The surviving animals were observed for 14 d after the day of dosing. All animals were subjected to gross pathological examination. Deaths were noted during the day of dosing and one day after dosing. Clinical signs of toxicity noted were ataxia, clonic and tonic convulsions, hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, loss of righting reflex, increased salivation, occasional body tremors and splayed gait. Surviving animals recovered one to five days after dosing. Surviving animals showed expected gain in bodyweight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study. Under the study conditions, the acute oral LD50 and 95% confidence limits of the test substance were calculated to be 1797 (1262 - 2560) mg/kg bw (Sanders, 2000).

Acute toxicity dermal

A study was conducted to determine dermal toxicity of the test substance (2-mercaptopropionic acid) according to OECD Guideline 402 and EC Directive 84/449. The acute dermal toxicity of the test substance was investigated in 5 male and 5 female Wistar rats. On the basis of the range finding results, each animal was given a single dermal administration of 2000 mg/kg bw as a 66.6% dilution. The pH was adjusted to 6.8 with a 25% ammonic solution. The skin was exposed to the test substance for 24 h and signs of erythema and oedema were subsequently evaluated once daily for 14 d. Clinical observations were conducted at regular intervals during the 14 d observation period. Body weights were measured on Days 0, 7 and 14. Gross pathological examinations were performed on animals at termination. No abnormal clinical signs were observed apart from a slight to moderate reduced activity in the animals. A very slight till well-defined erythema was observed in almost all of the animals for the entire observation period. Some animals had eschar on the skin and wrinkled skin 5 - 14 d post-administration (p.a.). No signs of oedema were observed. No pre-terminal deaths occurred. All animals showed normal weight gains. Gross pathological examinations at 14 d p.a. (terminal necropsy) revealed no test substance-dependent findings. Under the study conditions, the 14 d dermal LD50 was established at >2000 mg/kg bw in male and female rats (Kaufmann, 1990).

Justification for classification or non-classification

The acute oral LD50 value of the test substance was determined to be between 300 and 2000 mg/kg bw in Sprague-Dawley rats. According to the EU CLP (EC 1272/2008) criteria, the substance therefore warrants a classification as Acute Tox. 4 – H302 (Harmful if swallowed).