Mercaptoacetic acid, monoester with propane-1,2,3-triol

Endpoint summary

Description of key information

GMT is toxic if swallowed but non-toxic via dermal exposure. Inhalative toxicity was not determined because inhalation is not a relevant exposure route.

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:

05-Sep-1988 - 28-Feb-1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Credo, Les Oncins, 69210 L'Arbresle, France
- Age at study initiation: young adults, 5 to 7 weeks old
- Weight at study initiation: males: 177-218 g, females: 150 - 186 g
- Fasting period before study: 15 - 18 h
- Housing: By sex and in groups of 5 in polycarbonate cages of type MI of internal dimensions 365 x 225 x 180 mm
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

0.104, 0.122, 0.141, 0.164, 0.192 mL/kg bw administration of test article as supplied

Doses:

136, 160, 185, 210, 215, 252 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and abnormal clinical signs were noted 15 minutes after administration of the test article, then 1, 2 and 4 hours later and then daily during the 14 day study period. The animals were weighed on Day -1, Day 1 (immediately before administration of the test article), Days 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

Bliss's method and Lichfield & Wilcoxon's method used for LD50 calculation

Sex:

male/female

Dose descriptor:

LD50

Effect level:

172 mg/kg bw

Based on:

test mat.

95% CL:

153 - 193

Remarks on result:

other: by Bliss' method

Sex:

male/female

Dose descriptor:

LD50

Effect level:

181 mg/kg bw

Based on:

test mat.

95% CL:

162 - 201

Remarks on result:

other: by Lichfield & Wilcoxon's method

Mortality:

see table 1

Clinical signs:

other: - 136 mg/kg bw: Subdued behaviour was recorded in all the animals at 4 hours after treatment and prostration in one out of them on Day 2. - 160 mg/kg bw: Subdued behaviour was recorded in all the animals at 2 hours after treatment and prostration at 4 hou

Gross pathology:

Animals died during the study showed congested areas in the lungs and a pale aspect of the liver (at dose level of 210 mg/kg). No macroscopically noticeable abnormalities were noted when necropsying the rats killed at the end of the study (day 15).

LD50 calculated by Bliss' method was 172 mg/kg and 181 mg/kg calculated by Lichfield and Wilcoxon's method.

Table 1: Acute oral toxicity of GMT 75

Dose level [mg/kg]	Sex	# dead/ # treated	Total Mortality [%]
136	m	0/5	0
	f	0/5
160	m	2/5	60
	f	4/5
185	m	2/5	60
	f	4/5
210	m	2/5	50
	f	3/5
215	m	4/5	80
	f	4/5
252	m	4/5	90
	f	5/5

 

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The LD50 for GMT was 172 mg/kg calculated by Bliss' method and 181 mg/kg calculated by Lichfield and Wilcoxon's method.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

172 mg/kg bw

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

Study period:

01-Dec-2008 - 16-Feb-2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France 53940
- Age at study initiation: Within 8 - 12 weeks
- Weight at study initiation: 192 - 209 g
- Fasting period before study: no data
- Housing: The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fiber bedding
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: No less than 10% of the body surface was cleared for the application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Isotonic saline
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 0 (prior to the application) and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as the symptoms noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Signs of toxicity related to dose level used: Sighting study: Apathy, ataxia, extended hind legs, extended hind legs, tiptoeing, circular movements, abnormal posture, complete eye-closure, red tears from the eyes to the nose, and grooming were observed Ma

Gross pathology:

Effect on organs (related to dose level):
Sighting study: No treatment related effects were observed in any of the animals.
Main study: No treatment related effects were observed in any of the animals.

Table 1: Clinical observations

Animal no./ sex	Time of observation (post dose)	Observations
1 / female (sighting study)	30 minutes	Ataxia, extended hind legs
	1 hour	Apathy, ataxia, circular movements, extended hind legs, tiptoeing
	4 h 15 min	Apathy, ataxia, circular movements, extended hind legs, tiptoeing , red tears from the eyes to the nose
	23 hours	Apathy, complete eye closure, abnormal posture (Head and breast recumbent while hind legs standing)
	24 hours	Starting with grooming; (after patch removal)
	25 hours	Reddish swollen eyelids
	day 2	No findings
2 / female (main study)	2 hours	Red secretion at the nose
	4 hours	Red secretion at the nose, abnormal posture (head and breast recumbent while hind legs standing)
	days 1 - 7	skin irritation
	day 8	Red secretion at the nose
	day 9	No findings
3 / female (main study)	2 and 4 hours	Red secretion at the nose
	3 - 5 days	Skin irritation
	day 6	No findings
4 / female (main study)	30 min	Tiptoeing, vocalisation (slightly)
	2 and 4 hours	Red secretion at the nose, tiptoeing
	day l	Abnormal posture (head and breast recumbent while hind legs standing)
	days 2 - 13	Skin irritation
	day 14	No findings
5 / female (main study)	30 min, 2 hours	Secretion at the nose
	4 hours	Red secretion at the nose
	day 1	Abnormal posture (head and breast recumbent while hind legs standing)
	days 2 - 13	Skin irritation
	day 14	No findings

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The dermal LD50 was determined to be greater than 2000 mg/kg body weight. Therefore the substance is unclassified according to GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance meets the criteria for classification as Acute Oral Toxic Category 3 (H301) according to GHS.