3-mercaptopropionic acid

Endpoint summary

Description of key information

3-MPA is highly corrosive. Percutaneous toxicity cannot be determined because of the corrosivity of 3-MPA. High dose inhalation exposure caused irritation of the respiratory tract which finally led to mortality. 3-MPA is toxic if swallowed and harmful by inhalation. 

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

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline study; not GLP. Only 3 females per dose level. Classification is possible based on study results.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Only females were tested. Only 3 animals per dose were tested.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10%
- Amount of vehicle (if gavage): not reported
- Justification for choice of vehicle: water

MAXIMUM DOSE VOLUME APPLIED: not reported

Doses:

15.8, 31.6, 63, 126 or 252 mg/kg

No. of animals per sex per dose:

2-3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: periodic observations, pre- and post-dose weighing
- Necropsy of survivors performed: yes, 24 h post dose in one animal per group
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

120 mg/kg bw

Based on:

test mat.

Remarks on result:

other: probit model

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 63 - <= 126 mg/kg bw

Based on:

test mat.

Mortality:

see Table 1

Clinical signs:

other: No other signs of toxicity other than death were noted.

Gross pathology:

No visible lesions were found.

All animals survived following oral gavage doses of 15.8, 31.6 or 63 mg/kg.  Two of three died within 2 hours after
ingesting 126 mg/kg and all died within 1 hour after ingesting 252 mg/kg.
Using the probit model, the LD50 is approximately 120 mg/kg bw.
No signs of toxicity other than death were seen in these animals.  One animal from each of the three lowest dose
levels was necropsied 24 hours after exposure.  No visible lesions were found.  The surviving animals surpassed their
pre-exposure body weight by the end of the two week observation period.

 

Table 1: Acute oral toxicity of 3-MPA

Dose [mg/kg bw]	# dead / # treated	Time of Death
15.8	0/2	–
31.6	0/2	–
63	0/2	–
126	2/3	1 h, 2 h
252	3/3	less than 1 h

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

EU: T, R25
GHS: Acute Oral Category 3

Executive summary:

In an acute oral toxicity study similar to the later established OECD TG 401 2-3  female rats/dose were administered a single dose of 3-MPA at 10% in water at dose levels of 15.8, 31.6, 63, 126 or 252 mg/kg. Animals were observed for 14 days.

All animals survived following oral gavage doses of 15.8, 31.6 or 63 mg/kg. Two of three died within 2 hours after ingesting 126 mg/kg and all died within 1 hour after ingesting 252 mg/kg.
Using the probit model, the LD50 is approximately 120 mg/kg bw.
No signs of toxicity other than death were seen in these  animals. One animal from each of the three lowest dose levels was necropsied 24 hours after exposure. No visible lesions were found. The surviving animals surpassed their pre-exposure body weight by the end of the two week observation period.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

120 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

Study period:

2008-03-12 to 2008-04-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

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: Harlan-Winkelmann GmbH, Borchen (Germany),
- Age at study initiation: about 2 months
- Weight at study initiation: 182-199 g (m), 172-194 g (f)
- Fasting period before study: no
- Housing: During the acclimatization and study periods the animals were housed singly in conventional Makrolon Type IllH cages
- Diet (ad libitum): KLIBA 3883 pellets maintenance diet for rats and mice; PROVlMl KLIBA SA, 4303 Kaiseraugst, Switzerland
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2 °C
- Humidity (%): 20-80
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: March 12, 2008 to April 02, 2008

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas exposure tubes applying a directed-flow nose-only exposure principle.
- Exposure chamber volume: 3.8 L
- Method of holding animals in test chamber: plexiglass tubes
- Source and rate of air: Compressed air was supplied by Boge compressors
- Method of conditioning air: Air was conditioned (i.e. freed from water, dust, and oil) automatically by a VIA compressed air dryer.
- System of generating particulates/aerosols: Under dynamic conditions the neat test article was atomized into a baffle (pre-separator) from which the substance was conveyed into the intake of the cylindrical inhalation chamber. Atomization was achieved by using two types of binary nozzles with conditioned compressed air (15 L/min; dispersion pressure approximately 600 kPa). The test substance was fed into the nozzle by a calibrated digital pump (Harvard PHD 2000).
- Method of particle size determination: The particle-size distribution was analyzed using a BERNER-TYPE AERAS low-pressure critical orifice cascade impactor
- Temperature, humidity, pressure in air chamber: < 5%

TEST ATMOSPHERE
- Brief description of analytical method used: The test-substance concentration sampled by gravimetric analysis was eluted from the filter and then determined by HPLC. A sampling train was used to analyze volatilized test article in addition. No test article was found in the gass bubbler.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

860, 1350, and 2053 mg/m³ (0.86, 1.35, and 2.053 mg/L)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The appearance and behavior of each rat were examined carefully several times on the day of exposure and at least once daily thereafter. Body weights were measured before exposure, on days 1, 3 and 7, and weekly thereafter. Individual weights are also recorded at death, if applicable.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: rectal temperatures

Statistics:

Necropsy: pair-wise Fisher test after the R X C chi-squared test.
Body weights: one-way ANOVA
LC50: maximum-likelihood method (Bliss)

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 818 mg/m³ air

Exp. duration:

4 h

Mortality:

see Table 2

Clinical signs:

other: All exposure concentrations caused pronounced irritant effects in the upper respiratory tract (nose) and central nervous effects.  The following clinical signs were observed: bradypnea, irregular breathing patterns, tachypnea, labored breathing patterns, 

Body weight:

Comparisons between the control and the exposure groups revealed consistent, concentration-dependent decrease in body weights.

Gross pathology:

Animals sacrificed at the end of the observation period: The macroscopic findings were essentially indistinguishable amongst exposure and control groups. However, some rats showed evidence of inflammatory responses of the nose
Animals succumbing during the observation period: Eyes: opacity; nose: yellowishgreen discoloration, mucosa reddened; lung: less collapsed, light discoloration, dark red foci; stomach: bloated, glandular stomach: mucosa with light-red areas; small intestine: bloated, dark-red mucous content, mucosa reddened; liver, kidneys, and spleen: light discoloration.

Other findings:

Rectal temperatures were significantly decreased in both sexes at 750 ppm (p< 0.05) and in both sexes at 1200 and 2000 ppm (p<0.01).

Table 1: Test atmosphere characteristics

Group	1	2	3	4
Target conc [mg/m³]	control	750	1200	2000
Nominal conc [mg/m³]	--	978	1806	3283
Analytical conc [mg/m³]	--	703	1258	1904
MMAD [µm]	--	2.66	2.51	2.54
GSD	--	1.92	1.83	1.82
Aerosol mass < 3 µm [%]	--	57.6	61.7	61.2

 

Analytical as well as real-time aerosol monitoring of the aerosol test atmosphere from the breathing zone indicated
that the exposure conditions were temporally stable over the 4 hour exposure period.  The respirability of the aerosol
generated was verified (MMAD was < 4 µm; MMAD 2.5-2.7 µm; GSD 1.9).
All concentration data represented actual concentrations of the test substance in the rats' breathing zone. 

Table 2: Summary of acute inhalation toxicity

Group / sex	Target conc [mg/m³]	Toxicological Result^a	Onset and Duration of Signs	Onset and Duration of Mortality	Rectal Temperature
1 / m	0	0 / 0 / 5	–	–	38.1
2 / m	750	0 / 5 / 5	0d - 14d	–	33.1*
3 / m	1200	1 / 4 / 5	0d - 6d	0d	28.9**
4 / m	2000	2 / 4 / 5	0d - 7d	0d, 1d	27.4**
1 / f	0	0 / 0 / 5	–	–	38.2
2 / f	750	0 / 5 / 5	0d - 7d	–	34.7*
3 / f	1200	0 / 5 / 5	0d - 14d	–	32.9**
4 / f	2000	5 / 3 / 5	0d	0d, 1d	26.4**

m = males, f = females, * = p 0.05, ** = p 0.01

^aValues 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:

LC50 Inhalation (liquid aerosol, 4 h, m+f): approximately 1818 mg/m³
NO(A)EC: males and females: < 860 mg/m³
EU-Classification: Xn, R20-37
GHS-Classification: Acute Inhalation Category 4

Executive summary:

A study on the acute inhalation toxicity of 3-Mercaptopropionic acid (henceforward referred to as test substance) on rats has been conducted in accordance with OECD Guideline No. 403. Test procedures were adapted so as to comply also with the EU Directive 92/69/EEC, OPPTS 870.1300, and Japan MAFF, Notification No. 12 Nousan-8147. Three groups of rats were nose-only exposed to actual liquid aerosol in concentrations of 860, 1350, and 2053 mg/m³ air. The results can be summarized as follows:

LC50 (m+f) = 1.818 mg/L, NOAEC (m+f) < 0.860 mg/L

Mortality occurred in few rats at 1350 mg/m³ and above. All exposure concentrations caused pronounced irritant effects in the upper respiratory tract (nose) and central nervous effects. The following clinical signs were observed: bradypnea, irregular breathing patterns, tachypnea, labored breathing patterns, dyspnea, vocalization, breathing sounds, high-legged gait, salivation, nasal discharge (serous), nose: reddened, nose: swollen, nostrils/muzzle: red encrustations, nose: necrosis, piloerection, hair-coat ungroomed, behavioral changes (transient), exaggerated

response, fasciculations, convulsions (tonic), jerks, tremor, motility increased, motility reduced, limp, apathy, flaccidity (hindlegs), prostration, exophthalmia, miosis, chromodacryorrhea, cornea: opalescence, lens: opalescence, eyelids: red encrustations, cyanosis, emaciation, abdominal enlargement, hypothermia, decreased reflexes, and decreased body weights.

Internationally recognised 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 2.5-2.7 µm, GSD 1.9). NO(A)EC Males & females: <860 mg/m³ air

In summary, the aerosolized test substance (liquid aerosol of undiluted test article) proved to have a moderate to low acute inhalation toxicity in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 818 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

In an acute oral toxicity study similar to the later established OECD TG 401 2-3 female rats/dose were administered a single dose of 3-MPA at 10% in water at dose levels of 15.8, 31.6, 63, 126 or 252 mg/kg. Animals were observed for 14 days.

All animals survived following oral gavage doses of 15.8, 31.6 or 63 mg/kg. Two of three died within 2 hours after ingesting 126 mg/kg and all died within 1 hour after ingesting 252 mg/kg.
Using the probit model, the LD50 is approximately 120 mg/kg bw.
No signs of toxicity other than death were seen in these animals. One animal from each of the three lowest dose levels was necropsied 24 hours after exposure. No visible lesions were found. The surviving animals surpassed their pre-exposure body weight by the end of the two-week observation period.

 

Acute inhalation toxicity

In an acute inhalation toxicity study according to OECD TG 403, three groups of Wistar rats were nose-only exposed to 3-MPA as liquid aerosol in concentrations of 860, 1350, and 2053 mg/m³ air. The 4 h LC50 was 1.818 mg/L

Mortality occurred in few rats at 1350 mg/m³ and above. All exposure concentrations caused pronounced irritant effects in the upper respiratory tract (nose) and central nervous effects. The following clinical signs were observed: bradypnea, irregular breathing patterns, tachypnea, labored breathing patterns, dyspnea, vocalization, breathing sounds, high-legged gait, salivation, nasal discharge (serous), nose: reddened, nose: swollen, nostrils/muzzle: red encrustations, nose: necrosis, piloerection, hair-coat ungroomed, behavioral changes (transient), exaggerated

response, fasciculations, convulsions (tonic), jerks, tremor, motility increased, motility reduced, limp, apathy, flaccidity (hindlegs), prostration, exophthalmia, miosis, chromodacryorrhea, cornea: opalescence, lens: opalescence, eyelids: red encrustations, cyanosis, emaciation, abdominal enlargement, hypothermia, decreased reflexes, and decreased body weights.

Internationally recognised 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 2.5-2.7 µm, GSD 1.9). NO(A)EC Males & females: <860 mg/m³ air

In summary, the aerosolized test substance (liquid aerosol of undiluted test article) proved to have a moderate to low acute inhalation toxicity in rats.

 

Acute dermal toxicity

An acute dermal toxicity study does not need to be conducted because the substance is classified as corrosive to the skin.

Justification for classification or non-classification

LD50(oral) = 120 mg/kg bw

LC50(4h inhalalation, mist) > 1.8 mg/L

GHS classification: Acute Toxicity Oral: Category 3; H301: Toxic if swallowed. Acute Toxicity Inhalation: Category 4; H332: Harmful if inhaled.