Mercaptoacetic acid

Endpoint summary

Description of key information

In a study performed according to the OECD guideline # 401, the oral administration of mercaptoacetic acid to male and female Sprague-Dawley rats resulted to a LD50 of 73 mg/kg bw. The ammonium (71% solution) and sodium salts administered orally to male and female Sprague-Dawley or Wistar rats gave LD50’s between 25 and 200 mg a. i. /kg bw in OECD guideline # 423 studies. Behavioral abnormalities and in some cases, GI tract irritation, were the most common findings after oral administration. In a study performed according to the OECD guideline # 403, the exposure of male and female Wistar rats to a vapour/aerosol mixture of mercaptoacetic acid results in a LC50 of 1.388 mg/L. Clinical signs included a severe irritation of the respiratory tract and mucuous membranes and behavioural abnormalities, the lungs were discolourated at necropsy. However, a 7-hour inhalation exposure of male Sprague-Dawley rats to saturated vapours, generated at 125°C or ambient temperature, produced neither mortality nor clinical signs of toxicity. In a non-guideline acute dermal toxicity study, the LD50 of mercaptoacetic acid was 848 mg/kg bw in male and female New-Zealand white rabbits. The clinical signs were limited to skin irritation and necrosis at the sites of application.

 

Oral route

Mercaptoacetic acid and its ammonium and sodium salts are toxic by oral administration in rats. When expressed as mercaptoacetate anion, whatever the salt, or the concentration tested the LD50’s of the salts were in the range of the mercaptoacetic acid LD50.

 

In an acute oral toxicity study performed according to the OECD guideline # 401, 5 groups of 5 Sprague-Dawley rats per sex were dosed with 0, 40, 64, 80 and 200 mg/kg bw mercaptoacetic acid (purity 99%). Animals were observed for 14 days following the exposure for mortality and clinical signs. Mortality occurred at dose levels equal to and exceeding 64 mg/kg bw. Behavioural abnormalities (piloerection, lethargy, ptosis, prostration) were observed in all treated rats. The LD50 of mercaptoacetic acid was 73 mg/kg bw (Gardner, 1988).

 

The acute oral toxicity of ammonium and sodium mercaptoacetates was tested in male and female rats according to the Acute Toxic Class Method (OECD guideline # 423). The LD50 of the 71% aqueous solution of ammonium salt was between 50 and 200 mg/kg bw (equivalent to 35 and 142 mg/kg bw when expressed as active ingredient) in Sprague-Dawley rats (Hönack, 1996). Sodium mercaptoacetate was tested pure (>98%) or as a 46% aqueous solution in Wistar rats, the LD50’s were between 50 and 200 (Arcelin, 2000) or 200 and 500 mg/kg bw (equivalent to 92 and 230 mg/kg bw when expressed as a. i.) (Sanders, 2000), respectively.

 

Another study performed with ammonium mercaptoacetate according to the OECD guideline # 401 leads to an acute LD50 between 25 and 200 mg a. i. /kg bw in Wistar rats (Heusener, 1988).

 

Inhalation exposure

Mercaptoacetic acid is harmful by inhalation exposure. In an acute inhalation toxicity performed according to the OECD guideline # 403, 5 Wistar rats per sex and per groups were exposed nose-only for 4 hours to a respirable mercaptoacetic acid (purity > 99%) aerosol (particle size: 2.5-3.1 µm MMAD) at analytical concentrations of 0; 0.284; 0.837; 1.441 and 3.629 mg/l Animals were observed for 14 days following the exposure for mortality and clinical signs. Mortality occurred at exposure concentrations equal to and exceeding 1.441 mg/l. The clinical signs observed included respiratory distress (bradypnea, labored and irregular breathing patterns), nasal irritation (discharge and encrustations), corneal opacity and behavioral abnormalities (mobility reduced, limp, apathy, tremour, paralysis, prostration, reduced reflexes). The approximate LC50for males and females was calculated to be 1891 and 1094 mg/l, respectively and the combined LC50 is 1388 mg/m3. (Pauluhn, 2004).

 

In a non-guideline study, 2 groups of six male Sprague-Dawley rats were exposed in a 19-litre exposure chamber for 7 hours to vapours of mercaptoacetic acid (purity 98.2%). Air was bubbled at ambient temperature or at 125°C through mercaptoacetic acid and the vapours generated passed to the chamber. The nominal concentration of the atmosphere to which the animals were exposed was 620 ppm (2.4 mg/l) at room temperature and 8200 ppm (31.4 mg/l) at 125°C. The animals showed no untoward effect during the exposure or during a 2-week post-exposure observation period (Rampy, 1973).

 

Dermal route

In a non-guideline acute dermal toxicity study, 4 groups of 2 New Zealand white rabbits per sex were dosed with 250, 500, 1000 or 2000 mg/kg bw mercaptoacetic acid (purity 98.2%). Animals were observed for 14 days following the exposure for mortality and clinical signs. Mortality was 0/4, 1/4, 2/4 and 4/4 on day one. No other effects than a skin irritation at the site of application was reported. The LD50 was 848 mg/kg bw (Rampy, 1973).

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:

20 April to 19 May 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

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:

Test animals:
- Species: Rat Strain: Crl:CD(SD)BR
- Age: 4 to 6 weeks old
- Weight at dosing: 104-146 g
- Source: Charles River UK Lim., Margate, Kent UK
- Acclimation period: 7 days
- Diet: Labsure LAD 1, ad libitum
- Water: Tap water, ad libitum
- Housing: Animals were housed in groups by sex in stainless steel  suspended cages

Environmental conditions:
- Temperature: 23-26°C
- Humidity: 51 %
- Air changes: 15 air change/hour
- Photoperiod: Alternating 12-hour light and dark cycles

Rats were fasted overnight before treatment and 4 hours after treatment.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

40, 64, 80, 200 mg/kg

No. of animals per sex per dose:

40

Control animals:

no

Details on study design:

Animal assignment and treatment: Following a range-finding preliminary test, dose levels of 40, 64, 80 and  200 mg/kg were selected for the main study.  Five males and 5 females were assigned to each test groups. Following an  overnight fast, rats were given a single dose of thioglycolic acid by  gavage. The test substance was administered in distilled water at a  volume of 20 ml/kg bw. 

Animals were observed for gross toxicity,  behavioural changes and/or mortality soon after dosing and at frequent  intervals for the remainder of day 1 and at least once daily for the  remainder of the 14-day study. Body weights were recorded at day 1 (day  of dosing), 8 and 15 and at death. On day 14, surviving animals were  sacrificed and all animals were necropsied and examined for gross  pathological changes.

Statistics:

The LD50 was calculated using the method of Finney (1971) Probit analysis  (3rd Ed.) Cambridge University Press.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

73 mg/kg bw

Based on:

act. ingr.

95% CL:

67 - 81

Gross pathology:

Autopsy of rats that died revealed slight renal pallor in one male and female at 80 mg/kg.  Terminal autopsy findings were normal.

- Number of deaths at each dose level

                     Mortality
Dose level        Male                Female
(mg/kg)                
40                0/5                0/5
64                1/5                0/5
80                3/5                5/5
200               5/5                5/5
- Time of death : 
 200 mg/kg : 3 males & 3 females at 4 hours and 2 males and
2 females at 6 hours,  80 mg/kg : 2 males and 3 females at 5 hours, 1  female at 7 hours, 1 male and 1 female at 24 hours,  64 mg/kg : 1 male at  24 hours.

- Signs of reaction to treatment
-------------------------------------------------------------------
                 No. of rats in group of 5 showing signs
                 ----------------------------------------
Dose (mg/kg)               40         64         80         200
Signs                     M  F        M  F        M  F        M  F
-------------------------------------------------------------------
Piloerection              5  5        5  5        5  5        5  5
Hunched posture           5  5        5  5        5  5        5  5
Waddling                 5  5        5  5        5  5        5  5
Lethargy                 5  5        5  5        5  5        5  5
Pallor of
extremities               5  5        5  5        5  5        5  5
Decrease
respiration rate          2  0        5  5        5  5        5  5
Ptosis                    0  0        5  5        5  5        5  5
Prostration               0  0        1  0        4  2        5  5   
---------------------------------------------------------------------

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under these experimental conditions, the LD50 is 73 (67-81) mg/kg

Executive summary:

In an acute oral toxicity study performed according to the OECD guideline # 401, 5 groups of 5 Sprague-Dawley rats per sex were dosed with 0, 40, 64, 80 and 200 mg/kg bw thioglycolic acid (purity 99%). Animals were observed for 14 days following the exposure for mortality and clinical signs. Mortality occurred at dose levels equal to and exceeding 64 mg/kg bw. Behavioural abnormalities (piloerection, lethargy, ptosis, prostration) were observed in all treated rats. The LD₅₀of thioglycolic acid was 73 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September to November 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS
- Source: RCC, Ltd, Biotechnology & Animal breeding division,  Wölferstrasse, 4 CH-4414 Füllinsdorf , Switzerland.
- Age: 8-10 weeks
- Weight:  217.1-234.7 g (M), 158.9-181.9 g (F)
- Acclimatization: 1 week
- Housing: 3 per sex
- Diet: ad libitum Pelleted standard Kliba 3433, batch n° 03/00 and 04/00,  rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst)
- Water: ad libitum tap water

CONDITIONS:
- Air changes: 10-15/hour
- Temperature: 21-23.5 °C
- Relative Humidity: 36-57%
- Light-Dark cycle: 12/12

Route of administration:

oral: gavage

Vehicle:

other: Vehicle: bi-distilled water. Source: RCC Ltd Stability: stable under storage conditions. Storage conditions: at room temperature (20+/-3°C), away from direct sunlight

Details on oral exposure:

The animals received a single dose of the test item on a 200 , 50 or 25  mg/kg bw by oral gavage following fasting for approx. 17 hours, but with  free access to water. Food was provided again 3 hours after dosing. 

Doses:

25, 50 and 200 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Animals were observed once daily during the acclimatization phase and  then 1, 2, 3 and 5 hours after administration on day 1 and twice daily  for surviving animals during days 2-15. Surviving animals were weighted on day 1, 8 and 15. All abnormalities and  clinical signs were recorded. All animals were necropsied and examined macroscopically.

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

50 - 200 mg/kg bw

Based on:

act. ingr.

Mortality:

All males and females treated at 25 and 50 mg/kg survived until scheduled  necropsy. Two out of 3 females treated at 200 mg/kg died on day 1. The following animals were treated and percentage mortality was observed:                          
Males         Females
Group 1 (200 mg/kg)                 66%        
Group 2 (50 mg/kg)                 0%
Group 3 (50 mg/kg)        0%
Group 4 (25 mg/kg)                 0%
Group 5 (25 mg/kg)         0%

Clinical signs:

other: No clinical signs were observed during the observation period in all 50  mg/kg treated males and females and all 25 mg/kg treated females. Slightly ruffed fur was observed in all 200 mg/kg treated females from 1  to 3 hours (2 females) or from 1 or 5 ho

Gross pathology:

A distended stomach with gas was observed at the unscheduled necropsy in  two females treated at 200 mg/kg. No macroscopic findings were observed  at the other scheduled necropsy.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The median lethal dose is between 50 and 200 mg/kg in rat after a single oral administration in both sexes.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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:

ANIMALS
Unilever HsdCpb, WU
Breeder: F. Finkelmann, 33178 Borchen
Age: 6-9 weeks
Weight: 168 (153-185) g
Acclimatization: at least 7 days
Housing: no data
Diet: Altromin Standard Diät TPF N1324 ad libitum except during fastingWater: tap water ad libitum
Fasting: 17 hours before dosing and 4 hours after dosing

CONDITIONS:
Temperature: 21-22 °C
Relative humidity: 55-72 %
Light-Dark cycle (hours): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Doses:

200 and 25 mg/kg referring to active ingredient

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The test compound was solved in deionised water. Aliquots of 20 ml/kg body weight (bw) were administered once orally by gavage. The applied doses were 200 and 25 mg/kg bw referring to the active material. During a two weeks observation period, mortalities and clinical-toxicological observations were recorded daily.

The behaviour and general condition of all rats were monitored for at least 6 hours after the administration and then checked daily.All animals were weighted before treatment and on days 2, 4, 6, 8, 11, 13 and 15 of the experimental part.

All the rats died or were sacrificed at the end of the experimental part and necropsied and subjected to gross pathology examination.

Statistics:

not appropriate.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

25 - 200 mg/kg bw

Based on:

act. ingr.

Mortality:

At 200 mg/kg bw : all males and females were dead (5/5 and 5/5). Deaths occurred from 4 hours up to 7 hours after treatment.
At 25 mg/kg bw : no death (0/5 and 0/5)

Clinical signs:

other: Signs of intoxication were seen from 1-2 hours up to 24 hours after treatment. They comprised of locomotor disturbance, abdominal position and dyspnea. Pathological findings included black discolouration of the stomach and small intestine contents and fo

Gross pathology:

No macroscopic abnormalities were found in the animals sacrificed at the end of the experiment (25 mg/kg bw dose group).

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 is between 25 and 200 mg a.i./kg for males and females rats.

Executive summary:

The Acute oral toxicity of ammonium mercaptoacetate was evaluated in rats according to OECD N°401 guideline (Acute Toxic Standard Method). Groups of 5 male and 5 female Sprague Dawley rats were given a single oral dose of ammonium mercaptoacetate at doses of 25 and 200 mg/kg. Following treatment, rats were observed daily and weighted weekly. A gross necropsy examination was performed at the time of scheduled euthanasia (Day 14).

Ten animals died on day 1 after administration of 200 mg/kg (5 males and 5 females). Clinical signs observed were observed prior to death. Gross internal findings noted at necropsy for the dead animals were [reddish stomach and intestine, greenish-red mucoid contents, yellow red fluid contents in the bladde]. After administration of 25 mg/kg, no animal died.

Signs of intoxication were seen from 1-2 hours up to 24 hours after treatment. They comprised of locomotor disturbance, abdominal position and dyspnea.Body weight development of the treated animals was normal.Pathological findings included black discolouration of the stomach and small intestine contents and focal red discolouration of the glandular mucous membrane, emphysema and focal black discolouration ot the lung, and dilatation and extreme filling of the urinary bladder. No macroscopic abnormalities were found in the animals sacrificed at the end of the experiment (25 mg/kg bw dose group). The LD50 is estimated between 25 and 200 mg a.i./kg for males and females rats.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals:
Source: Fa. Harlan Winkelmann GmbH, 33178 Borchen
Acclimatization period: 15-21 days
Weight range at study initiation: 260-282 g (m), 189-206 g (f)
Fasting: 16 hours before dosing and 3-4 hours after dosing

Husbandry:
Housing: collective housing up to a maximum of 3 animals per cage (Makrolon type III)Illumination: artificial lighting from 7.00 a.m.-7.00 p.m.
Temperature: 22±3 °C
Relative humidity: 30-70%

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The acute oral toxicity of "Ammonium thioglycolate 71 %" was investigated according to a stepwise procedure in Wistar rats.
Three animals of one sex are used for each step.

On the basis of toxicity data from the test substance, a starting group of 3 female rats received a single oral administration of "Ammonium thioglycolate 71 %" in a dose of 200 mg/kg body weight. Based on the stepwise procedure, further groups using 3 females and 3 males each were treated with doses of 25 and 50 mg/kg body weight, respectively.

Doses:

25, 50, 200 mg/kg of the 71% ammonium thioglycolate solution

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Clinical observations were conducted at regular intervals during the 14-day observation period.
Gross pathological examinations were performed immediately on animals found dead and at termination on day 14 on surviving animals.
Body weights were measured at days 0, 7 and 14.

Statistics:

not appropriate

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 35 - < 142 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: active ingredient

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 50 - < 200 mg/kg bw

Based on:

test mat.

Remarks:

71% solution

Mortality:

All 3 female rats treated with 200 mg/kg body weight died pre-terminally. All animals of the other dose groups survived the whole observation period of 14 days.

Clinical signs:

other: All 3 rats treated with 200 mg/kg body weight showed severe clinical symptoms appearing 2 h post-administration and leading to death. All 3 female rats which received 50 mg/kg body weight exhibited alopecia on day 14 post administration. No other clinical

Gross pathology:

Gross pathological examinations on day 14 post administration (terminal necropsy) revealed no test article-dependent findings in the lower dose groups of 25 and 50 mg/kg body weight. In all 3 female rats which received 200 mg/kg body weight and died spontaneously, test article-dependent findings were observed.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The median acute lethal dose for rats of both sexes is:
- 50 < LD50 < 200 mg/kg bw for the 71% solution of Ammonium Thioglycolate
- 35 < LD50 < 142 mg/kg bw for the active ingredient (Ammonium Thioglycolate).

Executive summary:

The acute oral toxicity of ammonium mercaptoacetate was evaluated in rats according to the OECD N°423 guideline. A starting group of 3 female rats received a single oral administration of "Ammonium thioglycolate 71 %" in a dose of 200 mg/kg body weight. Based on the stepwise procedure, further groups using 3 females and 3 males each were treated with doses of 25 and 50 mg/kg body weight, respectively.

All 3 female rats treated with 200 mg/kg body weight died pre-terminally after exhibiting several signs of toxicity. All animals of the other dose groups survived the whole observation period of 14 days. At 50 mg/kg bw , animals exhibited alopecia on day 14 post administration. No other clinical symptoms were observed in any of the other rats treated.
The median acute lethal dose for rats of both sexes is estimated between 50 and 200 mg/kg bw for the "71% solution of Ammonium Thioglycolate" and between 35 and 142 mg/kg bw for the active ingredient "Ammonium Thioglycolate".

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS:
- Male and female Sprague Dawley rats CD (Crl: CD (SD) IGS BR)
- Supplier: Charles River (UK) Ltd, Margate, Kent, UK
- Weight: 221-229 g (M), 202-232 g (F)
- Age: 12 weeks
- Acclimatization:  at least 5 days
- Housing: groups of 3 by sex in solid-floor polypropylene cages
- Diet: ad libitum except fasting (Rat and Mouse Expanded Diet N°1, Special  Diets Services Limited, Witham, Essex, UK)
- Water: drinking water ad libitum
- Fasting: overnight before dosing and 3-4 hours after dosing

CONDITIONS:
- Temperature: 19-25 °C
- Relative Humidity: 30-70 %
- Air changes: approx. 15/hour
- Dark-Light cycle (hours): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Doses:

200, 500 and 2000 mg/kg sodium thioglycolate as 45.9% solution, equivalent to 92, 219 and 918 mg/kg sodium thioglycolate as active ingredient

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

All animals were dosed once only by gavage. The animals were observed for  death or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and  subsequently twice daily for up to 14 days. Individual body weights were  recorded prior to dosing and 7 and 14 days after treatment or at death. At the end of the observation period, animals were subjected to  macroscopic examination. No tissue was retained.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

92 - 229 mg/kg bw

Based on:

act. ingr.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

200 - 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 46% solution

Mortality:

Two animals treated with 2000 mg/kg and all animals treated with 500  mg/kg were found dead during the day of dosing or one day after dosing.  There were no deaths at a dose level of 200 mg/kg.

Clinical signs:

other: Common signs of toxicity noted at 2000 mg/kg were hunched posture,  decreased respiratory rate with hunched posture also commonly noted in  females at 200 mg/kg. Incidents of toxicity noted at  a dose level of  2000 mg/kg included laboured respiration and

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study  were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage or  epithelial sloughing of gastric mucosa and epithelial sloughing of the  non-glandular region of the stomach.

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information category 3 Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 of 16 December 2008

Conclusions:

The acute median lethal dose LD50 of sodium thioglycolate 46% solution was estimated to be in the range of 200-500 mg/kg (92-229 mg/kg as active ingredient).

Executive summary:

The acute oral toxicity of sodium thioglycolate 46% was evaluated in rats according to OECD N°423 guideline (December 17^th2001). Sodium thioglycolate 46% was administered by oral route (gavage at 200, 500 and 2000 mg/kg bw) to groups of 3 males and female Sprague-Dawley rats. Animals were then observed for 14 days.Two animals treated with 2000 mg/kg and all animals treated with 500 mg/kg were found dead during the day of dosing or one day after dosing. There were no deaths at a dose level of 200 mg/kg. Common signs of toxicity noted at 2000 mg/kg were hunched posture, decreased respiratory rate with hunched posture also commonly noted in females at 200 mg/kg. Incidents of toxicity noted at a dose level of 2000 mg/kg included laboured respiration and prostration, with hunched posture and ataxia noted at 50 mg/kg. Surviving animals recovered 2 days after dosing. No signs of systemic toxicity were noted in male animals at 200 mg/kg. All surviving animals showed expected gains in bodyweight. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage or epithelial sloughing of gastric mucosa and epithelial sloughing of the non-glandular region of the stomach.The acute median lethal dose LD50 of the sodium thioglycolate 46% solution was estimated to be in the range of 200-500 mg/kg (92-229 mg/kg as active ingredient).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

73 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

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:
- Species: Rat Strain: Wistar
- Age: ca. 2 months old
- Weight at dosing: ca. 200 g
- Source: Harlan-Winkelmann GmbH, Borchen (Germany)
- Acclimation period: at least 5 days
- Diet: Kliba 3883, ad libitum
- Water: Tap water, ad libitum
- Housing: Animals were housed singly in Makrolon type IIIH cages

Environmental conditions:
- Temperature: 22 +/- 2°C
- Humidity: 40-60%
- Air changes: ca. 10 air changes/h
- Photoperiod: 12h/12h

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Aerosol Generation and Exposure Technique:
- Mode of exposure:  Animals were exposed to the aerosolized test substance in Plexiglas  exposure tubes applying a directed-flow nose-only exposure principle. 
- Aerosol generation:  Under dynamic conditions the aqueous solution of the test article was  nebulized into a baffle (pre-separator) from which the substance was  conveyed into the intake of the cylindrical inhalation chamber. The test  article was nebulized using a binary nozzle with conditioned compressed  air. The solution was fed into the nozzle by a calibrated, digitally  controlled piston, equipped with a glass syringe.  Inhalation Chamber: The stainless steel directed-flow nose-only  inhalation chamber has the following dimensions: diameter = 30 cm  (two-chamber system), height = 28 cm (internal volume = about 7 L). 
- Inhalation chamber steady-state concentration:  The test atmosphere generation conditions provide an adequate number of  air exchanges per hour (ca. 129 x, continuous generation of test  atmosphere). Under such test conditions steady state is attained within  the first two minutes of exposure (t99% = 4.6 x chamber volume/flow rate;  McFarland, 1976). The ratio between the air supplied and exhausted was  chosen so that approximately 80-90% of the supplied air is removed via  the exhaust system. The remainder provides adequate dead-space  ventilation for the exposure tubes. At each exposure port a minimal air  flow rate of 0.75 l/min was provided. The test atmosphere can by no means  be diluted by bias-air-flows. The inhalation chamber was operated in a  well ventilated chemical fume hood.
- Air flows:  During the exposure period air flows were monitored continuously and, if  necessary, readjusted to the conditions required. 

Inhalation Chamber Temperature and Humidity:
Temperature and humidity measurements were made using a computerized  system. The values were recorded at intervals of 5 min.

Analysis of the Test Atmosphere:
- Nominal concentration:  The nominal concentration was calculated from the ratio of the total  quantity of test substance discharged during the exposure period and the  total throughput of air through the inhalation chamber.
- Gravimetric evaluation:  The test-substance concentration was determined by gravimetric analysis.  Filters were weighed immediately after cessation of sampling.  
- Analytical evaluation: Several samples were taken by bubbling the  inhalation chamber atmosphere through gas bubblers containing an aqueous  solution (0.04%) of phosphoric acid. The analytes were determined by  High-Performance Chromatography (HPLC).

Characterization of Aerodynamic Particle-Size Distribution:
The samples for the analysis of the particle-size distribution were also  taken in the vicinity of the breathing zone. During each exposure two  samples were taken. The particle-size distribution was analyzed using a BERNER-TYPE AERAS  low-pressure critical orifice cascade impactor (Hauke, Gmunden, Austria). 

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0, 284.1, 837.2, 1441 and 3629 mg/m3

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Body Weights:
Body weights were measured before exposure, on days 3 and 7, and weekly  thereafter. 

Clinical Signs:
The appearance and behaviour of each rat were examined carefully several  times on the day of exposure and at least once daily thereafter.

Rectal Temperatures:
The rectal temperatures were measured shortly after cessation of exposure  (approximately within ½ hour after the end of exposure) using a digital  thermometer with a rectal probe for rats.

Necropsy:
All surviving rats were sacrificed at the end of the observation period  and were subject to a gross-pathological examination.

Statistics:

Necropsy findings: pair-wise Fisher test after the R x C chi-squared  test. The Fisher test was only performed if differences occurred between  groups in the R x C chi-squared test or if a frequency value of < 5 was  calculated.  Body weights: one-way ANOVA (vide infra). Physiological data: ANOVA procedure (vide infra). Initial LC50 calculation by the author used moving average Interpolation according to  Scharper et al. (1994). LC50 was recalculated using a probit standard model.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 388 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

1 000 - 2 080

Exp. duration:

4 h

Remarks on result:

other: calculated with probit standard model

Sex:

male

Dose descriptor:

LC50

Effect level:

1 981 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

921 - 11 700

Exp. duration:

4 h

Remarks on result:

other: calculated with probit standard model

Sex:

female

Dose descriptor:

LC50

Effect level:

1 094 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

98 - 2 130

Exp. duration:

4 h

Remarks on result:

other: calculated with probit standard model

Mortality:

Mortality occurred at exposure concentrations equal to and exceeding 1441  mg/m³. In the range of the LC50-concentration, female rats appeared to be  more susceptible when compared to male rats. Mortality occurred up to the  first postexposure day.

Clinical signs:

other: Group 1: All rats tolerated the exposure without specific signs. Group 2/males: Nose: reddened. Group 3/males: bradypnea, labored breathing patterns, irregular breathing patterns, nose: reddened, nose: red encrustations, nostrils: red encrustations, pilo

Body weight:

Comparisons between the control and exposure group revealed transient changes in body weights at 837.2 and 1441 mg/m3 (see attached figure).

Gross pathology:

Animals succumbed during the observation period:  Nose: red; lung: less collapsed; dark-red marbled stomach: bloated, red  mucosa; intestines: bloated, reddish-mucous content, mucosa reddened;  liver: light coloured; spleen: light coloured; kidneys: bilaterally light  coloured; incisors: white discolouration; oral cavity: filled with  bedding material; oesophagus: filled with bedding material. Animals sacrificed at the end of the observation period: The macroscopic  findings in the exposure groups showed a low incidence of discolourated  lungs.

Other findings:

Reflex measurements
A battery of reflex measurements was made on the first post-exposure day. In comparison to the rats of the control group, male rats of group 4 and some female rats in groups 2-3 exhibited changes in the reflex behavior suggestive impaired reflexes in the first post-exposure day.

Rectal temperature
Mean values are shown in Table 2. Statistical comparisons between the control and the exposure groups 3-5 revealed significantly decreased the body temperatures shortly after cessation of exposure.

Table 1: Generation and characterization of chamber atmosphere (aerosolization of the neat test article) - Mean values

	Group 1	Group 2	Group 3	Group 4	Group 5
Target Conc. (mg/m³)	Control (air)	250	1200	1500	5000
Nominal concentration (mg/m³)^a	0	1408	5632	11440	35200
Gravimetric Conc. (mg/m³)	--	196.6	837.4	1542	3865
Analytical concentration (mg/m³)	--	284.1	837.2	1441	3629
Gravimetric:analytical (%)	--	69	100	»100	»100
Recovery (%)	--	20	15	13	10
Test article supply (ml/min)	--	16	64	130	400
Inlet Air Flow (l/min)	15	15	15	15	15
Exhaust Air Flow (l/min)	13	13	13	13	13
Temperature (mean,oC)	21.8	22.7	22.6	22.6	22.6
Rel. Humidity (mean, %)	< 6.5	< 5.4	< 5	< 5.2	< 5.3
MMAD (µm) GSD	-- --	2.48 2.20	2.85 2.15	2.77 2.01	3.07 2.01
Aerosol Mass < 3 µm (%)	--	59.8	53	54.6	49
Mass recovered (mg/m³)	--	136.7	799.2	1310	3926

MMAD = Mass Median Aerodynamic Diameter, GSD = Geometric Standard Deviation; -- = not applicable. Recovery: Analytical concentration relative to nominal concentration. a) For calculation a specific density D²⁰₄= 1.32 g/cm³ was used.

Table 2: Summary of acute inhalation toxicity - 4 hour exposure to aerosolized test substance

N Group /sex	Actual Concentration (mg/m³)	Toxicological Result	Onset and Duration of Signs	Onset of Mortality	Rectal Temperature (°C)
1 / m	0	0 / 0 / 5	--	--	37.6
2 / m	284.1	0 / 5 / 5	0d (5h)	--	37.3
3 / m	837.2	0 / 5 / 5	0d – 2d	--	35.3
4 / m	1440.9	1 / 5 / 5	0d–4d,7d–14d	1d	31.1*
5 / m	3628.8	5 / 4 / 5	0d	0d, 1d	28.7**
1 / f	0	0 / 0 / 5	--	--	38.4
2 / f	284.1	0 / 5 / 5	0d (5h) – 3d	--	37.5
3 / f	837.2	0 / 5 / 5	0d – 12d	--	36.9*
4 / f	1440.9	5 / 5 / 5	0d	1d	35.2**
5 / f	3628.8	5 / 5 / 5	0d	1d	28.8**

N = group assignment, m = males, f = females, * = p < 0.05, ** = p < 0.01

Values given in the 'Toxicological results' column are:

    1st = number of dead animals.

    2nd = number of animals with signs after cessation of exposure.

    3rd = number of animals exposed. 

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the calculations obtained by the Moving Average Interpolation procedure, the approximate combined LC50 for males and females is 1388 mg/m³.

Executive summary:

A study on the acute inhalation toxicity of THIOGLYCOLIC ACID on rats has been conducted in accordance with OECD Guideline No. 403, EU Directive 92/69/EEC, OPPTS 870.1300 and Japan MAFF, Notification No. 12 Nousan-8147. Four groups of rats were nose-only expo­sed to a mean aerosol concentrations of 284, 837, 1441, and 3629 mg/m³ air. The liquid aerosol generated (aerosolization of the undiluted test article) was respirable to rats and all

concentration data represent actual concentrations of the test substance in the rats breathing zone.Internationally recognized recommendations such as of SOT (1992) were fulfilled, in regard to the respirability of the aerosol generated, i.e. the MMAD was <4 µm (MMAD 2.5-3.1 µm, GSD»2.1).

Mortality occurred at exposure concentrations equal to and exceeding 1441 mg/m³. In the range of the LC₅₀-concentration, female rats appeared to be more susceptible when compared to male rats. Based on the calculations obtained by the probit standard modele, the approximate LC₅₀for males and females is 1891 and 1094 mg/m³, respectively, and the combined LC50 is 1388 mg/m3 . Mortality occurred up to the first postexposure day. The clinical signs observed included the following findings: bradypnea, labored breathing patterns, irregular breathing patterns, tachypnea, nasal discharge (serous), nose: reddened, nose: gray discolorations, nose: red encrustations, muzzle: red encrustations, nostrils: red encrustations, stridor, piloerection, hair-coat ungroomed, cyanosis, emaciation, motility reduced, limp, apathy, tremor (hind limbs), paralysis (all legs), high-legged gait, flaccidity (all limbs) , posture squatted, prostration, corneal opacity, tremor (entire body), reduced reflexes, decreased body weights, and hypothermia. The duration of clinical signs was governed by respiratory distress and behavioral abnormalities. At the end of the postexposure period most rats appeared to be clinically normal. Necropsy findings were suggestive that lung damage was causally related to mortality. .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 388 mg/m³ air

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

2 animals per dose levels

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Twenty-four hours prior to applying the test materials, the entire trunk  of the rabbits to be used were clipped free of hair with electric  clippers. The test materials were applied under a heavy gauge plastic  cuff. The cuff was held in place with rubber bands and covered with a  cloth bandage which was taped securely to the marginal hair. Thioglycolic  acid was applied as a solution in water.

Duration of exposure:

24 hours

Doses:

252, 500, 1000 or 2000 mg/kg

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

After application of the test material, the animals were placed in  individual holding cages with free access to food and water. At the end  of the 24-hour exposure period, the cuffs were removed and the skin was  washed with soap and water, rinsed thoroughly, and dried with a towel.  The animals were observed for signs of toxicity during the exposure and  periodically for two weeks or more thereafter. Body weights were recorded  before and after the exposure period and at intervals up to two-weeks  post-application or until the pre-exposure body weights were surpassed.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

848 mg/kg bw

Based on:

test mat.

95% CL:

505 - 1 430

Mortality:

Dose        # dead/# treated        Time of Death 
250         0/4                        --- 
500         1/4                        Day 1
1000         2/4                         Day 1, 1
2000         4/4                        Day 1, 1, 1, 1

Clinical signs:

other: Topical effects noted after removal of the cuff were slight to moderate  erythema, slight to moderate oedema and slight to moderate necrosis in  all cases (no other clinical signs were reported). 

Gross pathology:

no data

Interpretation of results:

Category 3 based on GHS criteria

Executive summary:

In a non-guideline acute dermal toxicity study, 4 groups of 2 New Zealand whiterabbits per sex were dosed with 250, 500, 1000 or 2000 mg/kg bw thioglycolic acid (purity 98.2%). Animals were observed for 14 days following the exposure for mortality and clinical signs. Mortality was 0/4, 1/4, 2/4 and 4/4 on day one. No other effects than a skin irritation at the site of application was reported. The LD₅₀was 848 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

848 mg/kg bw

Justification for classification or non-classification

REGULATION (EC) No 1272/2008:

* According to Annex VI Table 3.1 mercaptoacetic acid is classified:

- Acute oral toxicity: Toxic, category 3

- Acute inhalation toxicity : Toxic, category 3

- Acute dermal toxicity : Toxic, category 3

PROPOSED SELF-CLASSIFICATION:

According to the available acute toxicity data, and CLP criteria, mercaptoacetic acid should be classified:

- Acute oral toxicity: Toxic, category 3

- Acute inhalation toxicity : Harmful, category 4

- Acute dermal toxicity : Toxic, category 3