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Description of key information

The LD50 value of DMDS in the rat is between 50 and 300 mg/kg bw. The LD50-cut-off value according to OECD TG 423 was 200 mg/kg bw. DMDS should be classified as Acute Tox 3 - H301: Toxic if swallowed.


Study conducted according to OECD 403: Female and male Sprague Dawley rats were exposed to 4.8 mg/L aerosol composed of the test item (DMTP) in air. No mortality occurred. Signs were labored breathing, secretory responses and red/flaky skin, transient adverse effect on body weight. Thus; the LD50 is considered to be > 4.8 mg/L.


Study conducted according to OECD 403 including neurological examinations. Female and male Sprague Dawley rats were exposed to 4.2 mg/L aerosol composed of the test item (DMTP) in air. No mortality occurred. Signs were labored breathing, secretory responses and red/flaky skin, transient adverse effect on body weight, detailed neurological examinations showed a transient decreased muscle tone and reflexes as well as abnormal gait. Thus; the LD50 is considered to be > 4.2 mg/L.


Study conducted according to OECD 403 with neurological examinations. Female and male Sprague Dawley rats were exposed to 0.0021 mg/L decomposition products composed of the heated test item (DMTP) in air. No mortality occurred. Signs were labored breathing, nasal discharge and moist rales. No other adverse effects were reported. Thus, a LD50 value could not be established.


Study conducted according to OECD 402. Female and male New Zealand White rabbits were dermally exposed to DMTP at a concentration of 2000 mg/kg bw under occlusive conditions for 24h with a subsequent 14 days observation period. No mortality occurred. No significant dermal or systemic toxicity was seen throughout the study, gross postmortem observations were similar to those seen in control animals. Thus, the LD50 is considered to be > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 May 2012 - 13 Jun 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
yes
Remarks:
the study could have been terminated after 100% mortality in the 300 mg/kg group
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
yes
Remarks:
the study could have been terminated after 100% mortality in the 300 mg/kg group
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 161 - 185 g
- Fasting period before study: ca. 16 h
- Housing: in groups of 3 animals in MAKROLON cages on granulated textured wood
- Diet: Commercial diet, ssniff® R/M-H V1534, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 12-18
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2012-05-21 To: 2012-06-13
Route of administration:
oral: gavage
Vehicle:
other: 0.8% aqueous methylhydroxypropylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5, 30, 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
Doses:
50, 300, 2000 mg/kg bw
No. of animals per sex per dose:
3-6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed
before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after
administration. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - < 300 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
200 mg/kg bw
Based on:
test mat.
Mortality:
50 mg/kg bw: 0/6
300 mg/kg bw: 3/3 (death within 3 h post dose)
2000 mg/kg bw: 3/3 (death within 3 h post dose)
Clinical signs:
other: 50 mg/kg bw: revealed slightly reduced motility, slight ataxia, slight tremor, slightly reduced muscle tone and slight dyspnoea 300 mg/kg bw: slightly to moderately reduced motility, slight to moderate ataxia, slight to moderate tremor, slightly reduced
Gross pathology:
no pathological findings
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The LD50 value was ranked between 50 and 300 mg/kg bw. LD50-cut-off value according to OECD TG 423 was 200 mg/kg bw. DMDS should be classified as Acute Tox 3 - H301: Toxic if swallowed.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Effect level:
>
Based on:
test mat.
Remarks:
test material was heated to 100 °C in order to provide a vapour containing decomposition products of the test item
Exp. duration:
4 h
Remarks on result:
other: results obtained from Hoffman (1990) OECD 403 with decomposition products, no effect level derived due to the absence of permanent adverse effects
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.2 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: results obtained from Hoffman (1990) OECD 403 incl. neurological examinations
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.8 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: results obtained from Hoffman (OECD 403 first study)
Mortality:
None
Clinical signs:
other: mainly labored breathing, red/flaky skin, secretory responses
Body weight:

- other body weight observations: body weight losses were reported
Gross pathology:
no findings
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Based on the results for DMTP the LD50 value for inhalation is considered to be > 4.2 mg/L. According to Regulation (EU) No. 1272/2008 (CLP) the substance has to be classified as 'toxic if inhaled' (H331) Category 3.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
> 4.8 mg/L air
Physical form:
inhalation: aerosol

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no adverse effects observed at the dose tested
Mortality:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In the present study 4-mercaptomethyl-3,6-dithia-1,8-'octanedithiol was dermally administered to 10 New Zealand White rabbits (male/female) at a concentration of 2000 mg/kg bw. All animals survived throughout the study. The majority of animals exhibited weight losses or no weight change at Day 7 and/or 14. No significant dermal or systemic toxicity was seen throughout the study, although one animal exhibited ocular redness, discharge and opacity throughout the study. Gross postmortem observations were similar to those seen in control animals in this laboratory or were considered to represent normal physiological variations.Therefore, the dermal LD50 of the test item in rabbits is greater than 2000 milligrams per kilogram of body weight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw

Additional information

Justification for classification or non-classification

The LD50-cut-off value according to OECD TG 423 was 200 mg/kg bw. DMDS should be classified as Acute Tox 3 - H301: Toxic if swallowed.